Neoagaro-oligosaccharides　(NAOs)　belong　to　the　algae　oligosaccharides.　NAOs　have　been　found　to　have　diverse　biological　activities.　However,　the　effects　of　NAOs　on　depression　and　their　underlying　mechanism　have　not　been　thoroughly　studied.　A　chronic　restraint　stress　(CRS)-induced　C57BL/6J　mouse　model　was　used　to　assess　the　antidepressant　effects　of　NAOs.　Anxiety　and　depression　behaviors　were　assessed　by　open　field　tests　(OFT)　and　forced　swimming　tests　(FST),　while　interleukin　18　(IL-18),　5-hydroxytryptamine　(5-HT)　and　brain-derived　neurotrophic　factor　(BDNF)　were　the　molecular　biomarkers　of　depression.　Fecal　microbiota　transplantation　(FMT)　was　performed.　The　results　showed　that　NAO　treatment　significantly　improved　the　body　weight　of　depressed　mice　and　reduced　the　central　area　time　in　the　OFT　and　immobility　time　in　the　FST.　NAO　treatment　decreased　the　levels　of　IL-18　in　the　serum　and　increased　the　levels　of　5-HT　in　the　serum　and　whole　brain　and　of　BDNF　in　the　whole　brain.　NAO　treatment　mitigated　the　gut　microbiota　dysbiosis　in　the　depressed　mice　and　reversed　the　decreased　levels　of　short-chain　fatty　acids　(SCFAs)　in　the　cecum　of　the　depressed　mice.　FMT　indicated　that　the　gut　microbiota　is,　indeed,　linked　to　depression,　which　was　reflected　in　the　changes　in　weight　gain　and　behaviors.　In　a　word,　NAOs　effectively　reversed　the　CRS-induced　mice　model　of　depression,　which　depended　on　the　changes　in　the　gut　microbiota　and　SCFAs,　as　well　as　its　modulation　of　5-HT　and　BDNF.