Microorganisms in the gut microbiota have developed alongside the host for thousands of years. Spray-dried porcine plasma (SDPP) increases development and immunity, making it a promising antibiotic replacement. In this systematic review and meta-analysis, we examined all available data on spray-dried porcine plasma's immune response and microbiota composition alterations, which may affect antibacterial effectiveness. To achieve this goal, Cochrane central, ISI web of science (WOS), PubMed/Medline, Scopus, and EMBASE were systematically searched using standard terms. No language, study region, or research kind restrictions applied. Following the exclusion criteria, this meta-analysis included 11 papers on 474 animals' important traits. Eleven studies involved 474 animals in this meta-analysis. The study involved eight pigs, three mice, one dog, bird, and fish. Firmicutes, Bacteroidetes, and other bacteria were more prevalent in SDPP-fed pig samples than in control diet samples. Proteobacteria, Tenericutes, and Actinobacteria were less common in SDPP-fed pig samples. SDPP did not affect growth performance measures compared to the control group. SDPP-exposed animals had higher Shannon and Simpson indices and more species, regardless of BW. In addition, treatment groups had similar colonic microbiota richness estimators (Chao 1). This study represents the first comprehensive meta-analysis to investigate the impact of SDPP s on immune response and microbiota composition alterations, which may affect antibacterial effectiveness in the peer-reviewed literature. The study's findings demonstrated that the utilization of SDPP imposes little residual effects on the overall growth performance and increases the diversity and richness of bacterial communities, ultimately leading to alterations in the microbiota composition of the animals.