Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) coinfection present a significant challenge to global health, with complex interactions between these pathogens influencing disease outcomes and treatment responses. L-selectin, a key mediator of leukocyte trafficking and immune activation, has emerged as a crucial molecule in the pathogenesis of TB-HIV coinfection. This review aims to elucidate the role of L-selectin in TB-HIV coinfection, focusing on its implications for immune activation and disease outcome. We discuss the intricate interplay between TB and HIV in modulating L-selectin expression and function, as well as its impact on immune responses, disease severity, and treatment outcomes. Furthermore, we explore the potential of targeting L-selectin-mediated immune pathways as a therapeutic strategy for improving disease control and patient prognosis in TB-HIV coinfection.