C-type lectins (CTLs) are a family of carbohydrate-recognition domain (CRD)-containing proteins that bind to ligands in a calcium-dependent manner. CTLs act as important components of insect innate immune responses, such as pattern recognition, agglutination, encapsulation, melanization, phagocytosis and prophenoloxidase activation, as well as gut microbiome homeostasis maintenance, to defend against pathogens. Besides, some insect CTLs can facilitate pathogen infection and colonization. In this review, we describe the properties of insect CTLs and focus on explaining their role in viral, bacterial, parasitic and fungal infections.