Nanotechnology-based strategies can be useful tools to combat the alarming challenge of antibacterial resistance. Nanoparticles can be used as alternatives or supplementary in enhancing the effectiveness of the available drugs to control bacterial proliferation. Here, we evaluated the vibrant anti-proliferative role of silver nanoparticle (AgNPs; 31 ± 5 nm) against fish pathogen Pseudomonas aeruginosa (P. aeruginosa) to inhibit the infection in Labeo rohita. Fish was divided into four groups: control untreated (Con), 10 mg/l AgNPs exposed (NPs), P. aeruginosa challenged (Inf) and combinedly treated with AgNPs and P. aeruginosa (NPs + Inf). After 14 days of treatment changes in different bio-indicators including hemoglobin hematological parameters (hemoglobin, total erythrocyte count, hematocrit, total leukocyte count), biochemical parameters (total protein, albumin, globulin), oxidative biomarkers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)] and histological parameters of kidney and liver were observed. We found that infected fish (Inf) showed more symptoms of infection as compared to fish given combined treatment of AgNPs and P. aeruginosa (NPs + Inf). Aforementioned bio-indicators in AgNPs-exposed group (NPs) were comparable to control, showing that AgNPs were not toxic at this concentration. Our results thus show that AgNPs hindered the bacterial proliferation in challenged fish. This was further confirmed by CFU assays of muscle tissues collected from Inf and NPs + Inf groups. The finding of this study suggested AgNPs as potential candidates to prevent bacterial proliferation which could be beneficial for biomedical applications.