The transition from pregnancy to lactation is characterized by a progressive decrease in insulin sensitivity. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity. Recent studies suggest that plasma odd-chain fatty acids [OCFAs; pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0)] that inversely correlated with insulin resistance are synthesized endogenously from gut-derived propionate. The present study investigated the effects of soluble fiber during gestation on gut microbiota, plasma non-esterified fatty acids and insulin sensitivity in sows. Sows were allocated to either control or 2.0% guar gum plus pregelatinized waxy maize starch (SF) dietary treatment during gestation. The SF addition changes the structure and composition of gut microbiota in sows. Genus increased by SF addition may promote intestinal propionate production. Moreover, the dietary SF increased circulating levels of plasma OCFAs, especially C17:0. The SF-fed sows had a higher insulin sensitivity and a lower systemic inflammation level during perinatal period. Furthermore, the plasma C15:0 and C17:0 was negatively correlated with the area under curve of plasma glucose after meal and plasma interleukin-6. In conclusion, dietary SF improves insulin sensitivity and alleviates systemic inflammation in perinatal sows, potentially related to its stimulating effect on propionate and OCFAs production.