Malaria is a mosquito-borne disease which kills more than half a million people annually. This has made the search for novel anti-malarial agents to complement the current ones an issue of global importance. Capparis erythrocarpos is used to treat various diseases in traditional medicine. However, its anti-malarial activity and individual constituents of its leaf are not known. This study described anti-malarial activity of the 70% ethanol extract of C. erythrocarpos leaf (CEL) and its major constituent, betulinic acid (BA). BA was isolated from CEL and characterized using NMR and LC-MS spectroscopies. Anti-malarial activity was evaluated using the curative test against Plasmodium berghei in mice. CEL (30–150 mg/kg p.o.) and BA (10–25 mg/kg p.o.) significantly (P < 0.05) reduced Percentage parasitemia with anti-malarial activity of 42.26–72.86%. Lonart (10 mg/kg p.o), the reference drug, produced anti-malarial activity of 47.66%. CEL and BA also, increased (P < 0.05) WBCs, platelets, body weight loss and MST whereas, reducing RBCs and hemoglobin concentration. In conclusion, CEL and BA possessed remarkable anti-malarial activity by activation of the immune system and reversing thrombocytopenia without protecting against weight lost and anemia. CEL and BA could therefore be developed as new anti-malarial agents.