Background: Perimenopause is a transitional stage preceding menopause, characterized by hormonal fluctuations and physiological changes that may increase cardiometabolic risk. Emerging evidence suggests that the gut microbiome may influence these changes through estrogen metabolism and microbial metabolite production. Inulin, a prebiotic fiber that modulates the gut microbiome, may offer a targeted nutritional strategy; however, its effects during perimenopause remain largely unexplored. Objective: This proof-of-concept study evaluates the effects of short-term inulin supplementation on gut microbiome composition, microbial metabolites, vascular function, skeletal muscle health, and metabolic flexibility in perimenopausal overweight women or with obesity. Methods: We will conduct a randomized, blinded, placebo-controlled crossover trial among 27 women aged 40 to55 years. Participants will receive 10 g/day of inulin and a matched maltodextrin placebo for two 14-day intervention periods separated by a 2 to 4-week washout. We will assess changes in gut and vaginal microbiome composition and functional capacity, stool and plasma microbial metabolites, and circulating markers of estrogen metabolism as primary outcomes. We will also evaluate vascular function, skeletal muscle health and oxidative capacity, and metabolic flexibility as secondary outcomes. Additionally, we will assess physical activity, sleep, dietary intake, perimenopausal symptoms, and intervention feasibility, adherence, acceptability, and tolerability. Conclusion: This study will provide novel insights into the feasibility and biological effects of inulin supplementation on gut-host mechanisms and cardiometabolic health during perimenopause, informing the design of future larger-scale trials. Keywords: Gut Microbiome, Metabolome, Fiber, Women, Prebiotics, Clinical Trial Protocol, Inulin, Perimenopause, Healthy Aging