Objective This study aimed to investigate the impact of sciatic nerve transection on the gut microbiota in mice by establishing a sciatic nerve injury model and analyzing changes using 16S rRNA gene sequencing. Methods Eighteen C57BL/6 mice were randomly divided into six groups: sham-operated, and postoperative Day 1 (D1), Day 4 (D4), Day 7 (D7), Day 14 (D14), and Day 28 (D28) groups. Colonic contents were collected on days 0, 1, 4, 7, 14, and 28 post-surgery for 16S rRNA sequencing to assess alterations in microbial composition and predict functional changes in the gut microbiome. Results A clear temporal shift in the gut microbial community structure was observed following sciatic nerve transection. From Day 4 post-surgery, microbial richness and diversity showed a significant decline, indicating a disturbance in microbial homeostasis. By Day 7, partial recovery in community richness was noted, suggesting a transient adaptation phase. Taxonomic analysis revealed significant fluctuations in the relative abundance of dominant bacterial phyla, particularly Firmicutes, Verrucomicrobiota, and Proteobacteria. At the genus level, the abundance of Akkermansia progressively declined over time in the injury groups compared to the sham group, while Kurthia and Dubosiella demonstrated a notable increase starting on Day 4 and peaking on Day 7. These dynamic changes imply specific microbial taxa are responsive to peripheral nerve injury. Furthermore, PICRUSt-based functional predictions indicated that metabolic pathways involved in lipid metabolism, amino acid metabolism, and other essential microbial functions were significantly suppressed in the D7 group, coinciding with peak dysbiosis. These findings suggest a close association between nerve injury and gut microbial functional attenuation. Conclusions Sciatic nerve transection in mice induces pronounced and time-dependent alterations in the gut microbiota, both in taxonomic composition and metabolic potential. The decrease in beneficial genera such as Akkermansia, alongside the enrichment of potentially opportunistic bacteria like Kurthia and Dubosiella, reflects a shift toward a less favorable microbial environment. This dysbiosis is accompanied by reduced microbial metabolic activity, especially in key pathways related to host-microbiota interactions. These results highlight the bidirectional link between the nervous system and the gut microbiome. Targeting microbial imbalances may offer new strategies for promoting peripheral nerve repair and regeneration, potentially improving clinical outcomes following nerve injuries.