Previous studies on feeding grape by-products (GBP) to lambs have shown conflicting results regarding performance, nutrient digestibility, nitrogen metabolism, and blood constituents. To clarify these uncertainties, we conducted a systematic review and dose-response meta-analysis to evaluate the efficacy and dose-dependent effects of GBP in lamb diets. Sensitivity analyses were performed to assess the robustness of the results, including the localisation of knots, leave-one-out tests and the exclusion of data points with high GBP addition (more than 600 g/kg). The results showed that GBP addition had no statistically significant effect on DMI (P = 0.92), average daily gain (P = 0.21) or final live weight (P = 0.36). However, GBP inclusion had a significant effect on feed conversion ratio (P = 0.002), with lambs fed up to 450 g/kg GBP showing an improved feed conversion ratio, which peaked at 200 g/kg. ADF digestibility was not significantly affected by GBP inclusion (P = 0.08). Conversely, significant negative linear correlations were observed between the consumption of GBP and the digestibility of OM (P = 0.03), CP (P = 0.002), DM (P = 0.001) and NDF (P = 0.004). In contrast, the intake of GBP was positively associated with fat digestibility (P = 0.001). The meta-analysis revealed no significant association between GBP intake and urinary nitrogen excretion, nitrogen consumed, faecal nitrogen excretion, or nitrogen retained. Blood analysis also showed no significant correlation between GBP consumption and serum concentrations of albumin, cholesterol, glucose, triglycerides, or total protein. However, blood urea nitrogen concentration showed a significant non-linear, J-shaped relationship with GBP consumption (P = 0.001), decreasing with GBP inclusion up to 250 g/kg DM, with no significant changes at higher levels. No statistically significant effects of GBP on serum AST (P = 0.28) or GGT (P = 0.93) were observed. In contrast, GBP intake of up to 200 g/kg DM significantly reduced ALT activity in serum (P = 0.009). In conclusion, the intake of GBP shows a dose-dependent response that affects nutrient digestibility and may influence feed efficiency and health status of lambs. Intake of GBP in the range of 200-400 g/kg DM can improve feed conversion ratio and health but can also reduce the digestibility of certain feed components such as OM, DM, CP and NDF.