Background: The study aimed to assess if manual therapy, compared to ibuprofen, impacts the concentration of inflammatory factors, sex hormones, and dysmenorrhea in young women Methods: Thirty-five women, clinically diagnosed with dysmenorrhea, were included in the study. They were divided into group A—manual therapy (n = 20) and group B—ibuprofen therapy (n = 15). Inflammatory factors such as vascular endothelial growth factor (VEGF), C-reactive protein (CRP), prostaglandin F2α (PGF2α), E2 (PGE2) and sex hormones levels were measured. Dysmenorrhea assessed with the numerical pain rating scale (NPRS), myofascial trigger points, and muscle flexibility were examined before and after the interventions. Results: The difference in the level of 17-β-estradiol after manual and ibuprofen therapy was significant, as compared to baseline (p = 0.036). Progesterone levels decreased in group A (p = 0.002) and B (p = 0.028). The level of CRP was negatively correlated with sex hormones. Decrease in dysmenorrhea was significant in both groups (group A p = 0.016, group B p = 0.028). Non-significant differences were reported in prostaglandins, VEGF and CRP levels, in both groups. Conclusions: There were no significant differences in CRP, prostaglandins and VEGF factors after manual or ibuprofen therapy. It has been shown that both manual therapy and ibuprofen can decrease progesterone levels. Manual therapy had a similar effect on the severity of dysmenorrhea as ibuprofen, but after manual therapy, unlike after ibuprofen, less muscles with dysfunction were detected in patients with primary dysmenorrhea.