This study was carried out to evaluate combined and singular effects of ethanolic extract of Persian shallot (Allium hirtifolium Boiss) and synbiotic Biomin®IMBO on growth performance, innate immune responses, and antioxidant defense in zebrafish (Danio rerio). Fish with initial weight of 151.90 ± 0.31 mg were allocated in 21 10-L glass aquariums. The experimental groups were as follows: T1, control (without any supplementation); T2, 1% synbiotic; T3, 3% synbiotic; T4, 1% Persian shallot (as a medical plant); T5, 3% Persian shallot; T6, 1% Persian shallot and 1% synbiotic; T7, 3% Persian shallot and 3% synbiotic. At the end of the experiment (60 days), all treatments significantly showed higher final weight (FW), weight gain (WG), WG (%), and specific growth rate (SGR) compared with the fish fed on control diet. Furthermore, both synbiotic Biomin®IMBO and Persian shallot significantly improved intestine immune parameters including lysozyme, alternative complement hemolytic activity (ACH50), total immunoglobulin (total Ig), and myeloperoxidase (MPO) of zebrafish compared to fish fed on control diet (p < 0.05). Also, in all experimental groups, hepatic catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities significantly increased compared to the control group. Whereas, the highest MDA level was observed in the control group compared to the treatments (p < 0.05). Moreover, skin mucus immune parameters of zebrafish have been noticeably improved with synbiotic Biomin®IMBO and Persian shallot compared to fish fed on the control diet (p < 0.05). The results indicate that synbiotic or Persian shallot supplemented diet could enhance the general health status of the zebrafish.