Alfalfa should be avoided in people with allergies to members of the Fabaceae or Leguminosae plant families. Caution is warranted in individuals with grass allergies.

Alfalfa appears to be well tolerated by most individuals, although rare serious adverse effects have been reported.

Mild gastrointestinal symptoms may occur, such as stomach discomfort, diarrhea, gas, or larger/more frequent stools. Dermatitis (skin inflammation/redness) has been reported and may be due to alfalfa allergy.

Blood sugar levels may be reduced. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.

Lupus-like effects have been associated with alfalfa use, including antinuclear antibodies in the blood, muscle pains, fatigue, abnormal immune system function, and kidney abnormalities. Therefore, people with a history of lupus (systemic lupus erythematosus) or a family history of lupus should avoid alfalfa supplements.

Other rarely reported adverse effects include abnormal blood cell counts (pancytopenia) and lowered potassium levels (hypokalemia). In theory, thyroid hormone levels may be increased, gout flares may be stimulated, and estrogen-like effects may occur.

Contamination of alfalfa products with potentially dangerous bacteria (including Escherichia coli0157:H7, Salmonella, and Listeria monocytogenes) has been reported. In one case report, vomiting occurring after the consumption of seaweed and organic alfalfa was attributed to contamination of the capsules with high amounts of entospore forming and streptomyces-like bacteria. Copper, arsenic, and antimony have been found in alfalfa plants.

Many tinctures/liquid extracts contain high levels of alcohol and should be avoided when driving or operating heavy machinery.

Alfalfa supplements are not recommended during pregnancy and breastfeeding due to insufficient evidence and a theoretical risk of birth defects or spontaneous abortion. Amounts found in food are generally believed to be safe. Traditionally, alfalfa is believed to stimulate breast milk production, although this has not been well studied.

Tinctures/liquid extracts may contain high levels of alcohol and should be avoided during pregnancy.

A dose of 5-10 grams of dried herb three times daily has been taken by mouth.

Two tablets (1 gram each) of Cholestaid® (esterin processed alfalfa) taken by mouth three times daily for up to two months, then 1 tablet three times daily, has been recommended by the manufacturer.

A dose of 5 to 10 milliliters (one to two teaspoonfuls) of a 1:1 solution in 25% alcohol three times daily has been taken by mouth.

For treating high cholesterol, 40 grams of heated seeds prepared three times daily with food has been taken by mouth.

Alfalfa supplements in children are not recommended due to potential side effects.

Blood sugar levels may be reduced. Caution is advised when using medications that may also lower blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare provider. Medication adjustments may be necessary.

Alfalfa contains vitamin K, and therefore may reduce the "blood thinning" effects of the drug warfarin (Coumadin®). Alfalfa may add to the effects of cholesterol-lowering medications such as atorvastatin (Lipitor®) or simvastatin (Zocor®).

Alfalfa may increase the risk of severe sunburns when used with drugs that increase sun sensitivity, such as chlorpromazine (Thorazine®). Due to estrogen-like chemicals in alfalfa, the side effects of drugs that contain estrogens may be increased (such as birth control pills or hormone replacement therapy). In theory, alfalfa may increase thyroid hormone levels and may alter the effects of thyroid drugs such as thyroxine (Synthroid®, Levoxyl®).

Alfalfa may alter potassium and calcium levels like other drugs.

Many tinctures/liquid extracts contain high levels of alcohol and may cause nausea or vomiting when taken with metronidazole (Flagyl®) or disulfiram (Antabuse®).

Alfalfa may also interact with drugs that alter the immune system.

Blood sugar levels may be reduced. Caution is advised when using herbs or supplements that may also lower blood sugar such as aloe or bitter melon. Blood glucose levels may require monitoring, and doses may need adjustment.

Alfalfa may add to the effects of cholesterol-lowering agents such as fish oil, garlic, guggul, red yeast, and niacin.

Alfalfa has been reported to contain vitamin K, and therefore may reduce the effects of herbs and supplements that have blood-thinning effects that rely on depletion of vitamin K.

Because alfalfa contains estrogen-like chemicals, the effects of other agents believed to have estrogen-like properties, such as black cohosh, may be altered. Alfalfa may also alter thyroid levels in herbs such as bladderwrack.

Alfalfa may alter potassium and calcium levels. It may also interact with iron, vitamin E, and vitamin K.

Alfalfa may interact with therapies that alter the immune system or cause sun sensitivity.

Alfalfa may contain significant levels of zinc, copper, manganese, and selenium.