Objective: To evaluate the toxicological and psychotropic properties of Calotropis (C.) procera. Methods: C. procera leaves and root-bark aqueous extracts were evaluated for their toxic and behavioral effects using adult mice. Toxicity studies were carried out using Organisation for Economic Cooperation and Development guidelines 423 and 407 for acute and subacute evaluation. Behavioral studies were performed using traction test, fireplace test, hole-board test and forced-swimming test to evaluate the sedative, anxiety and depressive-like activities of the extracts. Results: Very low acute toxicity was observed in mice that received both leaves and root-bark extracts. The subacute test showed some morphological, biochemical and hematological changes in the treated groups. Behavioral assessment demonstrated anxiety effects on mice for C. procera leaf extract (400 mg/kg of body weight). Conclusions: The acute use of C. procera (leaves and root-barks) aqueous extracts could be considered as low toxic. However, their repeated uses could have harmful effect on some organs. Likewise, a single dose up to 400 mg/kg body weight of these extracts produce no sedative or depressive-like effect, but they possess possible dose dependent anxiety effect. Yet, more studies are necessary to relate these results to the chemical profile of the plant extracts.