Objective: The emergence of new infectious diseases and the increased in bacterial resistance to diseases have led to the search for potential sources of antimicrobials. Bivalves have been found to possess bioactive compounds that have tremendous potential in medical science. Corbicula fluminea and Geloina expansa are bivalves that can survive in extreme environmental conditions and are surrounded by various microbes; these may have facilitated the potential production of different bioactive compounds with unique features to protect against pathogenic microorganisms. Materials and Methods: Antimicrobial activity of various concentrations of the ethanolic crude extracts (ECEs) of C. fluminea and G. expansa were tested against bacteria and fungi using the standard disk diffusion technique. There were three bacteria used in the antibacterial assay, namely Escherichia coli (Gram-negative), Pseudomonas aeruginosa (Gram-negative bacteria), Staphylococcus aureus (Gram-positive), and for antifungal assay, the fungi, Candida albicans, and Aspergillus niger were used. Results: The ECEs of C. fluminea showed 12.67-h activity on E. coli with an inhibition zone (IZ) range of 10–12.8 mm and for G. expansa showed an IZ range of 9.6–14.4 mm. A similar IZ range for C. fluminea (10.6–12.4 mm) and G. expansa (9.8–13.6 mm) was observed in P. aeruginosa with an efficacy time of 14 h and 17.3, respectively. S. aureus test cultures also showed activity of C. fluminea ECEs with an IZ range of 0.00–17 mm and efficacy time of 15 h, while G. expansa showed a mean of 15.6 mm. The two fungal strains tested showed activity of C. fluminea, and G. expansa ECEs, an IZ range of 8.3–12.2 mm was observed in A. niger while C. albicans showed activity with an IZ range of 9.6–12.8 mm. The ECE's concentrations of 50 and 100 mg/ml of C. fluminea and G. expansa showed a significantly higher result than positive control against P. aerigunosa. Conclusions: The study showed that C. fluminea and G. expansa are potential sources of antimicrobial compounds. Identification, extraction, and purification of such compounds are recommended for future studies.