Tephrosia cinerea L. (Pers.) is a tropical species that exhibits antileishmanial activity in Leishmania amazonensis promastigote cultures and is commonly used to treat infections, inflammations, ulcers, nervous conditions, and diarrhea. However, no studies have investigated its effects on genetic material. Therefore, we evaluated the genotoxic potential, antigenotoxic potential, and cytotoxic effects of hydroalcoholic extracts of T. cinerea leaves. In an in vitro genotoxicity study, human peripheral blood leukocytes were treated for 3, 24 (comet assay), or 48 h (cell death assay) with 22, 44, or 88 μg/mL plant extract. In the in vivo assay, Swiss mice were treated with 500, 1000, or 2000 mg extract/kg body weight by intraperitoneal injection and were evaluated 24 h later.