The acute and subacute toxicity profile of the aerial extract of Monsonia angustifolia in Wistar rats was evaluated. The Organization for Economic Cooperation and Development (OECD) 420 guideline was adopted in the acute toxicity testing with a single oral dose of 5000 mg/kg (b.w.). For the 28-day daily oral dosing, the extract was administered at 75, 150, and 300 mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single dose of 5000 mg/kg b.w. the extract elicited no treatment-related signs of toxicity in the animals during the 14 days of experimental period. In the subacute toxicity, there was no significant difference in hematological, renal, and liver function indices. However, dose-dependent significant increases were observed on the plasma concentrations of white blood cell and platelet counts of the treated animals compared to the control group. While cage observations revealed no treatment-facilitated signs of toxicity, histopathological examinations of the kidneys and liver also showed no obvious lesions and morphological changes. These results suggest that the extract may be labelled and classified as safe and practically nontoxic within the doses and period of investigation in this study.