The rise of resistant strains poses a significant public health risk, particularly, in sub-Saharan Africa, where over 50% of global infectious disease-associated deaths occur, highlighting the urgent need for novel, safe, affordable, and accessible antimicrobials. Accordingly, we investigated the antimicrobial activity, cytotoxicity, and qualitative phytochemistry of the aqueous, hydroethanolic, and acetonic leaf, stem bark, and root bark extracts of Prunus africana (Hook. F.) Kalkman, based on its ethnomedicinal information. The results showed the aqueous root bark and aqueous/acetonic stem bark extracts demonstrated significant (p<0.05) antimicrobial efficacy against S. aureus at 800 µg/ml, outperforming other extracts and the reference antibiotic. Growth inhibition zones for most extracts on S. aureus showed a concentration-dependent increase, though not significantly (p>0.05) different. The acetonic root bark extract, particularly at 800 µg/ml, exhibited superior inhibitory effects against B. cereus compared to other extracts (p<0.05), although the positive control antibiotic significantly (p<0.05) outperformed all plant extracts. Notably, none of the studied extracts affected P. aeruginosa and E. coli, while varying effects were observed against C. albicans. Further we observed that the hydroethanolic and aqueous stem bark extracts' exceptionally low Minimum Inhibitory and Bactericidal Concentrations (MICs and MBCs) against S. aureus (3.125 µg/ml). Conversely, the acetonic leaf extract showed higher MIC and MBC values against S. aureus (100 µg/ml). Cytotoxicity assessments using brine shrimp nauplii revealed the percentage mortalities caused by Vincristine and aqueous root/stem bark extracts at 1000 µg/ml, were significantly (p<0.05) higher than those caused by other extracts (Median lethal concentrations (LC50) of 513 µg/ml to 24327.82 µg/ml). Qualitative phytochemistry identified alkaloids in root bark and stem bark extracts, flavonoids, phenols, quinones, steroids, and terpenoids across all samples, with saponins in acetonic root bark and all three leaf extracts, and glycosides in acetonic stem bark, hydroethanolic root bark, and acetonic leaf extracts. These findings highlight the diverse antimicrobial and cytotoxic properties of P. africana extracts, suggesting potential therapeutic applications and emphasise the need for further exploration.