Apical periodontitis (AP), a highly prevalent infectious disease driven by pathogenic microorganisms residing in periapical tissues, orchestrates a dynamic interplay between microbial virulence and host immune defenses. Emerging evidence indicates that these pathogens critically manipulate regulated cell death (RCD) pathways to subvert immune surveillance and dictate periapical bone remodeling outcomes. While RCD has traditionally been viewed as a dichotomy between pro-inflammatory destruction and anti-inflammatory repair, recent advances reveal its context-dependent duality, shaped by microbial-immune crosstalk. Despite growing interest in this field, current literature lacks a comprehensive synthesis delineating the dual-pathological impact of RCD mechanisms in AP progression, particularly their beneficial versus detrimental roles. This review critically evaluates the molecular mechanisms of RCD and crosstalk among its forms, delineating its dual roles in immune defense versus bone destruction during AP progression. We synthesize current understanding of RCD pathways in AP pathogenesis and explore therapeutically targeting these mechanisms to modulate disease outcomes. Furthermore, we explore the feasibility of developing therapeutic strategies for AP based on RCD targets and propose novel research directions to advance understanding and treatment of this condition.