<p>Short-chain fatty acids (SCFAs) are produced by microbes in the gut from macronutrient fermentation. As the key bacterial metabolites, three SCFAs—acetate, propionate, and butyrate—are abundant in the gut and are presently linked to a number of homeostatic and pathophysiologic immune regulatory processes. The significance of these metabolites in the control of numerous immunological processes is currently being closely examined especially in gut immunity in gut-liver and gut-brain axes. Besides affecting cell metabolism and functions that confer immunity to the host, interestingly, SCFAs are currently in the spotlight for their role in innate immune cell maturation and differentiation having potential translational benefits. Dysbiosis in the gut leading to alterations of gut microbe population affects wide array of physiologic functions including both local and systemic immune regulation. Affecting millions worldwide, inflammatory bowel disease (IBD) and colorectal cancer (CRC) are the major gut diseases where the etiology can be partially attributed to gut dysbiosis and short-chain fatty acid alterations. We closely monitored the impact of intervention strategies of IBD and CRC by alteration of gut microbiota through probiotic administration and fecal microbiota transplantation on innate immunity. Although ongoing studies underscore the implications of these strategies in combatting gut inflammation but the importance of SCFA metabolism on innate immunity needs to be addressed. With the current narrative, we aim to connect the dots and find any missing links, between how probiotic administration and fecal microbiota transplantation as therapies impact gut inflammation via innate immune cell regulation through SCFAs as gut microbial metabolites.</p>