Ethanolic extracts prepared from the leaves of Psidium guajava were evaluated for anti-trypanosoma and cytotoxicity activity in the bloodstream species of Trypanosoma brucei brucei (BS427) and HEK293 in 384-well Alamar Blue assays respectively. Cytotoxicity activity in HEK293 cells was subsequently used to estimate the selectivity index of the extracts. The activities of the plant extracts were determined to evaluate if further chemical and biological profi ling may be warranted for potential development in early drug discovery for African Sleeping Sickness. Two trypanocides, pentamidine and diminazene, were employed as reference drugs, while puromycin was also included as control for general cell growth inhibition. The results show that the extracts inhibited growth of T. b. brucei with an IC50 of 6.3 姯mL and 48.9 姯mL for 80% and 20% ethanolic preparations respectively, with corresponding activity of less than 50% against HEK293 at the highest screening dose of 238.10 姯mL. The estimated selectivity index of the extracts compares favourably with pentamidine and diminazene. Meanwhile the reference compounds were found to have activities in agreement with published sensitivities at the doses screened. The lack of cytotoxicity at the doses screened and direct activity against T. b. brucei whole cells, make these extracts suitable candidates for further chemical elucidation and biological profi ling.