Macroalgae are profoundly present in the intertidal regions of oceans and have been consumed as human diet for several decades. Dietary glycans derived from macroalgae have incredible powers to keep the equilibrium of the human gut microbiome. So far, it has been confirmed that the human gut bacteria possess a unique cluster of genes that are dedicated for utilizing a specific type of glycan. Some genes of those clusters consist of endo-acting enzymes that yield a diversity of oligosaccharides in vivo. In vivo-produced oligosaccharides are often reckoned by immune cell receptors and play a crucial role in gut homeostasis. Some molecular mechanisms by which human gut bacteria utilize macroalgal glycan have been discovered in the past couple of decades. Notwithstanding, studies based on human gut bacteria and nutraceuticals suggest that we should unravel glycan-utilizing mechanism of every microbial strain present in gut microbiota. This will devise innovative nutraceutical strategies to decisively manipulate the gut microbiota for improving human health. Thus, this chapter critically summarizes known molecular mechanisms of human gut bacteria by which they are utilizing macroalgal-derived glycans.