This study examines the potential defending effects of the diatom, Amphora coffeaeformis, as a feed additive versus the deleterious effects (mainly on gonads) caused by microplastics (MPs) in Nile tilapia, Oreochromes niloticus. Groups of male tilapia were pre-fed diets with four different supplementation levels of A. coffeaeformis (0%, 2.5%, 5%, and 7.5%) for 70 days, then exposed to 10 mg/L MPs for 15 days. Thereafter, samples were taken from the four experimental groups and the control fish group, for evaluating blood picture, erythrocytes alterations, biochemical parameters, catalase (CAT), superoxide dismutase (SDO), and total antioxidant capacity (TAC). In addition, male reproductive performance was assessed by quantifying the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T), also testicular sections and GSI% were also assessed. The results showed that the number of erythrocytes were significantly (p < 0.05) higher, but the number of red blood cells (RBCs), the level of Hemoglobin (Hb), the percentage of Hematocrit (Ht), the number of platelets, and the eosinophil percentages were significantly decreased (p < 0.05) when fish exposed to MPs. Biochemical parameters (ALP, glucose, uric acid, albumin, and A/G ratio) were significantly increased after MP exposure compared with the control group. Furthermore, MPs induced a significant decline in both serum LH and T levels. Testicular, histological, degenerative changes and testis-ova were found in the MP-exposed fish. Thus, A. coffeaeformis supplementation displayed ameliorative properties that detoxified the negative effects of MPs. This study provides a better understanding of the reproductive injuries caused by MPs exposure and evidence for the use of A. coffeaeformis as a natural remedy in freshwater tilapia.