Objective To investigate the clinical effect of Huoxue Neiyi Prescription in the treatment of endometriosis dysmenorrhea and its effect on interleukin-6 (IL-6) and prostaglandin F2α (PGF2α). Methods A total of 60 patients with endometriosis dysmenorrhea were randomly divided into observatiion group and control group, with 30 patients in each group. The patients in the observation group and control group were orally given granules of Huoxue Neiyi Prescription and desogestrel and ethinylestradiol tablets (Marvelon), respectively, since day 5 of the menstrual cycle for 21 consecutive days. The two groups were compared in terms of clinical outcome, as well as dysmenorrhea score and serum levels of carbohydrate antigen (CA125), IL-6, and PGF2α before and after treatment. Results There was no significant difference in the distribution of clinical outcomes between the two groups (P>0.05). Before treatment, there was no significant difference in dysmenorrhea score between the two groups (P>0.05), and after treatment, both groups had a significant reduction in dysmenorrhea score (P<0.05). There was no significant difference in the level of CA125 between the two groups before and after treatment (P>0.05). Before treatment, there were no significant differences in the levels of IL-6 and PGF2α between the two groups (P>0.05); the control group showed no significant changes in the levels of IL-6 and PGF2α after treatment (P>0.05), while the observation group had significant reductions in the levels of IL-6 and PGF2α after treatment (P<0.05). Conclusion Huoxue Neiyi Prescription can effectively decrease the degree of endometriosis dysmenorrhea, reduce the release of inflammatory factors, and alleviate pain, with few adverse effects.