Microplastic particles exhibit multiple toxic effects, disrupting physiological processes in fish, such as Nile tilapia (Oreochromis niloticus), a widely cultured species. Probiotics could help counter polyamide microplastic toxicity while promoting fish health and sustainable aquaculture. A 6-week experiment was conducted on Nile tilapia included four treatments: (1) without polyamide microplastics and/or probiotics (control) and (2) with polyamide microplastics (PA-MP), (3) probiotics (Pr.), or (4) polyamide microplastics and probiotics (PA-MP + Pr.). The outcomes demonstrate that exposure to polyamide microplastics caused poorer growth performance and survivability along with reduced hemoglobin, and upregulated glucose levels, which were restored by probiotics application. The prevalence of erythrocytic abnormalities increased in the polyamide microplastic group but probiotics supplementation reduced the anomalies. Fish exposed to polyamide microplastics exhibited a lower frequency of goblet cells than other groups. Moreover, expression of antioxidant genes (SOD and CAT) and immune genes (IL-1β, IFN-γ, and TNF-α) was higher during polyamide microplastic exposure, which was downregulated in the polyamide microplastics along with probiotics group. These findings suggest that multi-species probiotics relieve microplastic-induced stress and hindrance of growth in Nile tilapia, which will help sustainable aquaculture practices safeguard fish health and maintain aquaculture productivity by alleviating adverse impacts of microplastic pollution in waterbodies.