Microplastic (MP) pollution threatens aquatic ecosystems and food safety, yet organ-specific contamination in tropical estuarine fish remains largely unexplored. In Bangladesh, where fish is a vital protein source, such assessments are critically lacking. This study quantified MPs in two commercially important catfishes, Pangasius pangasius and Mystus gulio (n = 60), from the Meghna Estuary, and assessed ecological and human health risks. MPs were extracted from gills, digestive tracts, and muscles and characterized by microscopy and FTIR. Results showed tissue-specific patterns, with higher loads in gills and digestive tracts than in muscles. Mean abundance was significantly greater in P. pangasius (38.7 ± 10.1 items) than in M. gulio (23.9 ± 7.3 items). Fibers < 0.5 mm, mostly violet, were dominant. Ecological risk indices revealed higher values for P. pangasius across all metrics: Polymeric Hazard Index (2006 vs. 1340), Risk Index (160 vs. 101.5), and Pollution Load Index (1.71 vs. 1.34), indicating substantial polymer-related risks and contamination level. Nylon posed the greatest hazard in P. pangasius (risk level, Eᵢ = 127.3), reflecting its persistence and adsorptive potential. Human exposure was higher from P. pangasius (2.44 particles/day for adults; 2.35 for children) than from M. gulio, confirming tissue- and species-specific risks.