Abstract The aim of this study was to investigate in vitro antioxidant properties and in vivo protective effects of the methanol extract of the Hypericum triquetrifolium Turra (HT) seed against acute hepatotoxicity, myelotoxicity and hematotoxicity in rats induced by cyclophosphamide (CP). In order to investigate in vivo protective effects of the HT extract on rat tissues, the rats were divided into nine groups. The toxic effects of CP and the protective effects of HT extract on nucleated cells that are produced by bone marrow, serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and oxidative stress index (OSI) levels were investigated biochemically. Additionally, liver tissue samples were examined for histopathological changes and apoptosis by Bcl-2, Bax and caspase-3 immunohistochemistry. The results of this study show that HT seed methanol extract has high total phenolic content (179.52 μg GAE/mg) and antioxidant activity (87.48% in 500 μg/mL concentration). CP administration caused hepatotoxicity, myelotoxicity and hematotoxicity in the rats. Whereas, the groups of rats that were injected with different concentrations of HT (25, 50 and 100 mg/kg) and CP (150 mg/kg) showed significant protective effects on bone marrow nucleated cells and important decreases on serum ALT, ALP, LDH and OSI levels were observed when compared with the CP injected group.