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Using protein-restriction diets becomes a potential strategy to save the dietary protein resources. However, the mechanism of low-protein diets influencing pigs&#8217; growth performance is still controversial. This study aimed to investigate the effect of protein-restriction diets on gastrointestinal physiology and gut microbiota in pigs. Eighteen weaned piglets were randomly allocated to three groups with different dietary protein levels. After a 16-week trial, the results showed that feeding a low-protein diet to pigs impaired the epithelial morphology of duodenum and jejunum (<i>p</i> &lt; 0.05) and reduced the concentration of many plasma hormones (<i>p</i> &lt; 0.05), such as ghrelin, somatostatin, glucose-dependent insulin-tropic polypeptide, leptin, and gastrin. The relative abundance of <i>Streptococcus</i> and <i>Lactobacillus</i> in colon and microbiota metabolites was also decreased by extreme protein-restriction diets (<i>p</i> &lt; 0.05). These findings suggested that long-term ingestion of a protein-restricted diet could impair intestinal morphology, suppress gut hormone secretion, and change the microbial community and fermentation metabolites in pigs, while the moderately low-protein diet had a minimal effect on gut function and did not impair growth performance.