Mannose is a natural monosaccharide that plays a central role in host–pathogen interactions and has emerged as a versatile scaffold for designing anti-infective agents. This review summarizes recent advances in mannose-based glycoconjugates with antibacterial, antiviral, antifungal, and antiparasitic activity. In bacteria, FimH antagonists prevent Escherichia coli adhesion, while mannose-functionalized materials disrupt Pseudomonas and Burkholderia biofilms or enhance delivery of anti-tubercular drugs. In virology, mannose-containing dendrimers, glycopolymers, and nanoparticles inhibit HIV, SARS-CoV-2, Ebola, HPV, and HSV by targeting viral glycoproteins or blocking lectin-mediated transmission. Mannose-decorated vaccines and nanocarriers also show promise against fungal pathogens and parasites. Continued optimization of presented structures could lead to the promising candidates for clinically applicable therapies.