Background: The Premenstrual syndrome (PMS) encompasses a range of physical, emotional, cognitive, and behavioral symptoms that occur periodically during the luteal phase of the menstrual cycle, resolving shortly after menstruation begins, in the absence of underlying medical or psychiatric conditions Objective: Objective of the study is to assess the knowledge regarding premenstrual syndrome among adolescent girls across three high schools of Gujrat. Methodology: A descriptive cross-sectional study was conducted among 173 adolescent girls from three high schools in Gujrat—GGHSS Ghareeb Pura, GGHS Municipal Model, and GGHS MB Fatima Jinnah—over a period of four months (July to September 2025). Participants were selected using a convenient sampling technique based on inclusion criteria of age 12–17 years, attainment of menarche, school enrollment, and willingness to participate. Data were collected using a structured, pre-tested questionnaire assessing demographic characteristics and knowledge of Premenstrual Syndrome (PMS). Each correct response was scored as one mark, and knowledge levels were categorized from poor to excellent. Ethical approval, written informed consent, and confidentiality were ensured. Collected data were analysed using SPSS version 25, employing descriptive statistics (frequencies and percentages) and chi-square tests to examine associations between knowledge and demographic variables. Results: A total of 173 high school girls participated, mostly aged 14–15 years, with nearly equal representation from 9th and 10th grades and three schools. Overall knowledge of Premenstrual Syndrome was low, with 59.5% having poor knowledge, and no significant association was found between knowledge and age, school, or grade, indicating a substantial knowledge gap. Conclusion: The study revealed that the majority of high school girls had poor knowledge regarding Premenstrual Syndrome. No significant association was found between knowledge level and age, school, or grade, highlighting the need for targeted educational interventions.