Matrine (MT) and oxymatrine (OMT), two kinds of alkaloid components found in the roots of Sophora species, have various pharmacological activities and are demonstrated to have anti-inflammatory, anti-allergic, anti-virus, anti-fibrotic, and cardiovascular protective effects. They are recently proved to have anti-cancer potentials, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- or radiotherapy-induced toxicity when combined with other chemotherapeutic drugs. In this review, we summarize the recent investigations regarding the anti-cancer activities and possible molecular targets of MT and OMT for cancer prevention and treatment in order to provide clues and references for further study.