Purpose The aim of the study was to evaluate the effects of nutraceuticals containing Equol, Resveratrol, Quecitine and Passiflora (Zemiar (R), Avantgarde, Pomezia, Rome, Italy) on quality of life (QoL) and sexual function in perimenopausal women. Methods Sixty perimenopausal women having vasomotor symptoms and being in the -1, +1a of the STRAW system (amenorrhea for longer than 60 days and FSH < 20 UI/L) were enrolled. The modified Kupperman Index (KI) was used to evaluate menopause symptoms. The Short Form-36 (SF-36), Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to assess QoL, sexual function and sexual distress, respectively. The study had two follow-ups at 3 and 6 months. Results The women reported an improvement in the KI total score from the baseline (35 +/- 4) to the 1st (21 +/- 3, p < 0.05) and the 2nd (18 +/- 2, p < 0.01) follow-ups. At the 1st follow-up, the women reported QoL improvements in some functions (p < 0.05); at the 2nd follow-up, they reported improvements in all categories (p < 0.001). At baseline, the total FSFI score was 23.1 +/- 1.2 and the FSDS score was 18.1 +/- 1.4, both indicating sexual dysfunction with sexual distress. FSFI and FSDS total scores did not change at the 1st follow-up (p = NS). On the contrary, at the 2nd follow-up, the FSFI score had risen to (27.6 +/- 1.5) (p < 0.001) and the FSDS score had dropped to (11.3 +/- 1.2) (p < 0.001). Conclusion Nutraceuticals can be effective in modulating the perimenopausal symptoms in women. The progressive reduction of the vasomotor symptoms reported by women over the nutraceutical usage could contribute to improve their QoL and sexual life.