Native Americans use sagebrush leaves to treat colds and sore eyes. Native women historically used it to ease childbirth and relieve cramps. Early Spanish Californians knew the plant as “Romerillo”, and regarded it as a panacea, using it in tea for bronchial troubles, or as a wash for wounds and swellings. They ate the seeds and fruits raw or pounded into a meal for cooking. Pioneers commonly placed sagebrush leaves in mattresses to repel fleas and bed bugs. The California Sagebrush has a very distinctive pungent odor and is sometimes referred to as 'cowboy cologne'. This plant relies on wildfire for seed germination and burned plants can keep growing.

It is often claimed to secrete chemicals into the ground which inhibit other plants from growing near and around the shrub. The leaves are also reported to have been chewed fresh, or dried and used for smoking, mixed with tobacco and other dried leaves. (Bean and Saubel 1972). The Luiseno tribe reportedly burned the bushes with white sage in ceremonial fires before hunting (Sparkman 1908). May cause skin rashes. This plant continues to be used medicianally by Native Americans and others.