Purpose: The perimenopausal period is marked by hormonal fluctuations that trigger a complex interplay between estrogen levels and neurotransmitters’ function, contributing to increased susceptibility to depression and anxiety in women. Concurrently, hormonal changes, coupled with alterations in vaginal tissue, lead to sexual dysfunction during this transitional phase. This study aimed at evaluating the association between menopausal symptoms and sexual dysfunction among perimenopausal women and identifying the mediating effects of depression and anxiety on this association. Patients and Methods: Data for the present cross-sectional study were collected from participants via Arabic versions of three questionnaires; the modified Menopausal Rating Scale (MRS), the Female Sexual Functioning Index (FSFI) and the Hospital Anxiety and Depression scale (HADS). Results: Our study was conducted on 149 females with age ranged from 45 to 55 years. On studying the relation between modified MRS and HADS, the menopausal symptoms were significantly high among female with high anxiety scores. Regarding the relation ship between MRS and FSFI, women with anxiety and physical and mental exhaustion had significantly lower FSFI scores than women without such symptoms (19.2 [2–31.4] vs 21.7 [3.8–30.9], p = 0.04, respectively). Furthermore, there were statistically significant negative correlations between depression scores and sexual desire (r = −0.32, p < 0.001), arousal (r = −0.25, p = 0.003), and total FSFI scores (r = −0.27, p = 0.04). Conclusion: Perimenopausal women experience a confluence of challenges related to depression, anxiety, and sexual dysfunction. Understanding the interconnectedness of hormonal and psychosocial factors is essential for tailored interventions aimed at improving mental health and sexual well-being during this transitional phase.