Giardiasis remains a significant global health burden, constrained by limited diagnostic tools, the emergence of drug-resistant Giardia lamblia strains, and the absence of a licenced human vaccine. To address these critical gaps, this review provides a comprehensive functional analysis of the Giardia proteome, emphasizing molecular targets essential for the parasite’s survival and pathogenesis. We systematically examine the structural proteome, specifically the tubulin reservoir and the diverse giardin family (α-, β-, γ- and δ-giardins), elucidating their indispensable roles in the ventral disc attachment mechanism. Beyond structural components, we detail the ‘pathoproteome’, and moonlighting enzymes, highlighting how the secretome – including cathepsin B-like cysteine proteases (notably giardipain-1) and variant-specific surface proteins facilitate immune evasion and host intestinal epithelial damage. Furthermore, the review explores the metabolic and encystation proteomes, identifying unique enzymes such as carbamate kinase and fructose 1,6-bisphosphate aldolase that offer high therapeutic selectivity. By synthesizing these proteomic insights, this work identifies high-priority candidates for the development of next-generation therapeutics, prophylactic, and diagnostic interventions aimed at mitigating the global impact of this neglected disease.