The class of structurally and functionally diverse MOCs that are easily assembled through coordination-driven self-assembly is particularly intriguing due to their chiroptical characteristics, distinct chiral phenomena, and chemical tunability. The examples presented in this review showcase the potential of rational chemical manipulations in exploring large and complex metal-organic cages (MOCs) as mimics of biological systems. These MOCs can be utilized in various applications, ranging from sensing to catalysis, thanks to the generation of subtle chiral microenvironment created via coordination. However, there remains a substantial gap in our understanding of the mechanisms underlying the effects of chirality and the most effective approaches for exploring resulting biochemical and biomedical applications.