Supplementation of post-weaning diets with exogenous enzymes has been suggested to control post-weaning syndrome, by compensating for the under-developed endogenous enzyme secretory capacity and increasing nutrient digestibility in newly weaned pigs. The effect of in-feed enzymes in improving gut maturation, growth and/or health in weaned piglets is not always consistent. A systematic review and a meta-analysis were therefore conducted to determine which exogenous enzymes are most consistent in improving piglet growth and digestibility when supplemented to post-weaning diets. The mean difference effect of enzyme supplementation on growth and digestibility of dry matter (DM), gross energy (GE), crude protein (CP), and P digestibility was calculated for each study and this was used as the effect size estimate in the meta-analysis. The impact of feed enzyme supplementation on intestinal health and bone mineralization was also discussed where information was available in the literature. From a total of 90 studies included in the meta-analysis, gain to feed ratio (G:F) was improved in 55, remained un-changed in 28 and deteriorated in 7, in response to enzyme supplementation. Average daily gain, average daily feed intake and G:F was improved when phytase was supplemented in the diet. Phosphorous digestibility was increased with phytase supplementation while GE digestibility was reduced. Dietary phytase supplementation increased bone mineralization in pigs fed diets with a reduced P content. Supplementation with multi-enzyme complexes increased DM and CP digestibility. In conclusion, the most consistent improvements in piglet growth, P digestibility and bone mineralization were found due to exogenous phytase supplementation. Supplementation with xylanase alone or in combination with β-glucanase had inconsistent effects on piglet growth and nutrient digestibility. The most consistent improvements in growth and nutrient digestibility due to supplementation with multi-enzyme complexes were found when mannanase and/or protease were included in the complex.