Polycystic ovary syndrome (PCOS) is the most prevalent multifactorial endocrine disorder which affects 6% to 20% of females which are of reproductive age, depending on diagnostic criteria. The symptoms typically evident during early adolescence are irregular menstrual cycles, anovulation, and acne. Although promising developments have been made in PCOS over the past decades, the distinct etiologies and pathophysiology of this syndrome are not fully revealed. Various contributing factors to the development of PCOS were precisely examined, including epigenetic mechanisms, unhealthy lifestyles, environmental poisons, tension, nutrition, inflammation, oxidative stress, obesity, insulin resistance, and hyperandrogenism. Recent studies suggest that endoplasmic reticulum stress plays a major role in the development of PCOS. It has been observed that NLRP3 inflammasome is activated in PCOS and is responsible for chronic inflammation and metabolic disturbances. This review illustrates the relationship between ER stress and activation of NLRP3 inflammasomes and investigates the therapeutic targets that regulate endoplasmic function and reduce inflammation. The endoplasmic reticulum generates numerous reactive oxygen species, which stimulates the activation of the NLRP3 pathway responsible for the pathogenesis of various metabolic and reproductive disturbances in PCOS. In this review, we will discuss the natural and synthetic drugs that reduce endoplasmic reticulum stress and prevent the initiation of NLRP3 inflammasomes. This review emphasizes that approaches for PCOS are pivoting toward personalized therapies, genetic and epigenetic approaches, and stem cell therapies to generate effective treatments. These approaches may have more potential to improve the metabolic and endocrine functions of PCOS.