Context Phytase plays a crucial role in the nutrition of piglets. Incorporating phytase into weaner pigs’ diet may alleviate the anti-nutritional effect by catalyzing the hydrolysis of phytic acid. As a result, bounded phosphorus and other minerals become more available for absorption, thereby enhancing nutrient utilization growth performance. Aims This study evaluated the efficacy of dietary phytase supplementation on the performance of weaned piglets. Methods Two hundred and forty cross-bred piglets (Yorkshire × Landrace × Duroc), of initial average bodyweight (BW) of 5.57 ± 1 kg at weaning, were assigned to five dietary treatments in a complete randomized block design. The study was conducted in the following three phases: Phase 1 (Days 1–7), Phase 2 (Days 8–21), and Phase 3 (Days 22–35). The treatments included basal diet containing 0.15% lower concentration of both total calcium and total phosphorus (NC), a standard basal diet (PC), NC + 500 phytase units per kilogram of feed (NC500), NC + 1000 phytase units per kilogram of feed (NC1000), and NC + 1500 phytase units per kilogram of feed (NC1500). Key results In Phase 1, the final BW was higher (P < 0.01) in PC and the phytase-supplemented diets than in the NC treatment. In Phase 2, Phase 3, and the overall days the average daily gain (ADG) and gain-to-feed ratio (G:F) were greater (P < 0.05) in the PC and the phytase-supplemented diets than in the NC treatments. The ADG and G:F were also higher (P < 0.01) in the phytase-supplemented diets than in the NC treatment. The digestibility of calcium, phosphorus, and blood myo-inositol was higher (P < 0.05) in the phytase-supplemented diets than in the NC treatment in Phase 2. In Phase 3, the level of blood myo-inositol was higher (P < 0.01) in the phytase-supplemented diets than in NC. Fecal inositol hexakisphosphate was lower (P < 0.01) in the phytase-supplemented diets than in NC in both Phases 1 and 2. Conclusion Dietary supplementation of phytase increased the digestibility of phytate by releasing phosphorus, calcium, and myo-inositol concentration, leading to improved growth performance. Implications Inclusion of phytase in pig diets can help farmers save money on feed additives such as phosphorus, improve environmental sustainability, and promote better growth performance.