The gallbladder is an important component of the hepatobiliary system and exhibits several anatomical variations that may have significant clinical and surgical implications. Variations such as Hartmann’s pouch, Phrygian cap deformity, septate gallbladder, and diverticula are often asymptomatic but may predispose individuals to bile stasis, gallstone formation, inflammation, and biliary obstruction. The present study analyses morphological variations of the human gallbladder observed in cadaveric specimens and correlates these anatomical findings with biochemical markers and potential protein involvement in gallbladder disease progression. Emphasis is placed on proteins involved in bile metabolism, inflammation, extracellular matrix remodelling, and cholesterol transport, which may contribute to gallstone formation and gallbladder structural changes. The study further proposes a hypothesis linking mucin proteins, inflammatory cytokines, and fibrosis-related proteins to the development of Hartmann’s pouch, bile stasis, and gallstone formation. Additionally, a medical informatics framework is proposed for integrating anatomical, biochemical, proteomic, and imaging data to develop predictive models for gallbladder disease and surgical risk assessment. Understanding the relationship between anatomical variations and protein expression patterns may help in early diagnosis, personalized treatment strategies, and improved surgical planning. This study highlights the importance of integrating anatomy, biochemistry, proteomics, and medical informatics to better understand gallbladder diseases and their complications.