BackgroundHealthcare professionals and educators closely monitor the occurrence of climacteric symptoms in women's primes. Knowledge and perception of menopause play a crucial role in improving quality of life. This study aimed to assess the knowledge and perceptions of menopause among Saudi women and identify its predictors. This study is the first of its kind in the southern region of Saudi Arabia. MethodsConducted in accordance with the STROBE guidelines, this cross-sectional study was carried out in the Jazan region from May 2022 to January 2023 and involved 480 Saudi women who provided consent. Data were collected through interviews using a validated questionnaire and random sampling. The questionnaire consisted of four parts: informed consent, demographics, 21 knowledge questions, and ten menopause perception questions. The validity of the content and the internal consistency were evaluated before data collection. Primary healthcare centers were randomly selected from four governorates with a proportional sample size to the population. Descriptive analysis, Pearson correlation, and multivariate logistic regression analyses were performed using IBM-SPSS. ResultsAmong the participants, 64 % were under 40 years old, 80 % had experienced menarche between the ages of 10 and 15, 48 % were employed, approximately half held a bachelor's degree, and they had a good family income. The mean knowledge score of the participants was 48.87 ± 11.72, with a minimum score of 27 and a maximum score of 78. In terms of knowledge categories, 56.3 % of the participants (N = 270) were classified as having low knowledge, while 43.8 % (N = 210) were classified as having high knowledge. Most of the participants had positive perceptions and agreed that menopause is a natural event in women's lives. There was a significant positive correlation between knowledge and perception (R = 0.219, P < 0.01). Variable findings were observed regarding the role of explanatory variables in women's knowledge of menopause between univariate and multivariate models. The results of the multivariate model showed that age (46–50 years, OR = 0.42), having children (OR = 1.09), residence (OR = 0.45–5.73) and family income categories (medium: OR = 3.98, good: OR = 3.78, and excellent: OR = 1.95) had a significant impact on knowledge, highlighting the correlation between demographic factors and knowledge. ConclusionsBased on the study findings, we recommend implementing workplace and community-based activities to increase women's awareness of menopause and incorporating it as an integral part of counseling sessions for women in this age group. Therefore, the results of the study will be shared with the relevant authorities responsible for women's health, enabling them to effectively support and educate women.