The key challenge of bio-monitoring is to explore comprehensive knowledge of bio-indicator organisms and to understand their responses to environmental alterations such as heavy metal pollution. The present study aimed for assessing the diversity of sediment-dwelling molluscs and their responses to different heavy metals in the sediment and water of the Shitalakshya River. Classical taxonomic analysis of Molluscan fauna revealed 16 species under 8 families of two major classes, Gastropoda and Bivalvia. There was a clear variation in the species-wise abundance of both molluscs but the overall abundance of both invertebrate groups did not vary significantly across the sites (p>0.05). Among ten heavy metals (Cr, Cd, As, Ni, Pb, Mn, Cu, Zn, Co, and Se), the concentration of Mn was relatively higher than other metals in both water and sediment samples. In contrast, the lowest concentration was also observed for Cd and Se. Mollusca abundance showed positive correlation with heavy metals except for chromium. Furthermore, GLM model confirmed the strong negative relationship (p<0.05) of Pb) with Molluscs, respectively. Overall, these results have implications for the biodiversity assessment of aquatic macroinvertebrates as well as their uses in monitoring the health of river ecosystems of Bangladesh.