Curcumin exhibited numerous key activities including antioxidant, anti-inflammatory, and immunostimulatory effects in fish. This study evaluated the protective effects of curcumin (CUR) against lead (Pb)-induced toxicities in fish. Healthy Cyprinus carpio L. individuals were segregated into control, Pb only, Pb+CUR, and CUR only groups. Pb groups were exposed to 1 mg L of Pb, and CUR groups were fed a basal diet supplemented with 15 g kg of CUR. After eight weeks, growth performance, Pb accumulation in tissues, various haemato-biochemical parameters, immune responses, and cytokine gene expression were measured. Dietary CUR effectively decreased Pb accumulation in tissues and increased the survival of Pb-exposed fish. Co-treatment with Pb and CUR reversed alterations in haemato-biochemical parameters, ameliorated Pb-induced oxidative stress, enhanced immune responses, and restored intestinal enzymatic activities. Dietary CUR reversed changes in intestinal microbiota in Pb-exposed fish. Pb-induced upregulation of NF-κBp65 and HSP70 was inhibited by dietary CUR. CUR supplementation upregulated the mRNA levels of SOD, Nrf2, IL-10, and CYP450 1A and attenuated Pb-induced degradation of I κB-α mRNA levels. Overall, CUR antagonizes Pb-induced negative impacts in fish. Thus, dietary CUR had several beneficial effects on immune responses, decreased Pb accumulation in tissues, and reversed Pb-induced oxidative stress in fish. Therefore, CUR plays a protective role in Pb-induced immune toxicity in fish, and, as such, may be suitable as an aqua feed additive for use in carp aquaculture.