Marine fauna provides a plentiful repository of peptides and bioactive proteins. Peptides and proteins isolated from marine animals have been studied and applied in the development of food supplements, drugs, and cosmeceutical products because of their special bioactivities, such as anti-inflammatory and antioxidant effects. This study focused on exploring the alleviating effects of five major marine animal-derived peptides (Apostichopus japonicus, Acaudina leucoprocta, Melanogrammus aeglefinus, Phascolosoma esculenta and Rhopilema esculentum) on adjuvant-induced arthritis (AIA). The treatment with five marine animals-derived peptides downregulated the expression levels of pro-inflammatory cytokines of interleukin (IL)-1β, IL-17 and tumor necrosis factor (TNF)-α in the bones of the mice with AIA and alleviated the rough surface of bone tissues significantly. A. japonicus-treatment ameliorates inflammation by restoring nuclear factor-κB pathway in AIA mice. High-throughput sequencing of the gut microbiota based on 16S rRNA sequencing revealed that A. japonicus peptide-treated AIA mice showed alterations and imbalance of intestinal flora and an increased abundance of Lactobacillus and Clostridium. Furthermore, metabolomic analysis showed that the level of short-chain fatty acids (SCFAs) in the feces was enhanced to different degrees in mice treated with five major marine animal-derived peptides. Taken together, we propose that major marine animal-derived peptides can alleviate arthritis by improving the imbalance in the gut flora and increasing SCFAs production to varying degrees.