Background Pre-menstrual syndrome (PMS) is a condition associated with altered hormone levels during the menstrual phase of females and is characterised by physical, emotional, and behavioural symptoms that have a negative impact on the quality of life of females. The symptoms of PMS may vary between individuals, but the major complication is pain, especially during menstrual days. The current treatment strategy involves the use of hormonal therapies and analgesics for symptomatic relief, but these therapies have a risk of potential side effects. The use of herbal and nutraceutical supplements in PMS conditions is increasing due to their long-term safety and proven efficacy. The current real-world study aimed to evaluate the efficacy and tolerability of Ezedayz® tablets containing Vitex agnus-castus extract (EVX40™), vitamin B6, and magnesium in PMS subjects. Methodology A real-world, open-label study was conducted involving 64 participants with varied severity of PMS symptoms. Participants were categorised into Group A (N=23) receiving standard therapies, Group B (N=20) receiving Ezedayz®tablets, or Group C (N=21) receiving standard and Ezedayz®therapy. Standard therapies were provided as per physician supervision, and Ezedayz® tablets were given for 90 days. All subjects were evaluated on core symptoms of PMS like menstrual backache, menstrual cramps, joint or muscle pain, and headache using the numerical rating scale (NRS), and quality-of-life (QoL) was evaluated using a QoL questionnaire. A spontaneous reporting methodology was used to evaluate the tolerability of the therapies provided. Statistical analysis was performed as per the statistical plan. A p-value of <0.05 was considered statistically significant. Results Out of 64 participants, five were lost to follow-up, and the data of 59 participants were included in the final analysis. All groups showed improvement in all evaluated parameters, but Group B and Group C showed greater improvement at the end of the study in all evaluated parameters. The quality-of-life assessment revealed greater improvement in Group B and Group C participants compared to Group C in all evaluated QoL parameters. No serious side effects were observed in any subjects. Conclusion The results of the current study conclude that the nutraceutical composition of Vitex agnus-castus extract, vitamin B6, and magnesium is effective in reducing the severity of PMS symptoms and improving the quality of life of PMS subjects. The nutraceutical therapy provided greater relief from PMS symptoms compared to standard therapy alone, and this effect was augmented when the nutraceutical therapy was provided in combination with standard therapies. Similarly, the improvement in quality-of-life parameters was greater in subjects treated with nutraceuticals alone or in combination therapy. Despite the limitations of the study, the results of the current study are promising, and the nutraceutical composition (Ezedayz®) can be effectively used in clinical settings to control symptoms and improve the quality of life of PMS patients.