Tetramethylpyrazine (TMP) has been confirmed to suppress inflammation in endometriosis (EMs). Herein, this study investigated whether and how TMP affected NLRP3 inflammasomes and oxidative stress in EMs. After establishment of an EMs rat model, rats were treated with different concentrations of TMP. The size of endometriotic lesions and the latency and frequency of torsion in rats were recorded, followed by the measurement of relevant indicators (TNF-α, IL-6, IL-2, IL-10, MDA, SOD, GSH, CAT, ROS, NLRP3, ASC, GSDMD, caspase-1, Nrf2, and HO-1). The study experimentally determined that TMP treatment markedly decreased the size of endometriotic lesions and improved torsion in rats with EMs. The levels of inflammatory proteins, oxidative stress markers, NLRP3 inflammasome, and pyroptotic proteins were elevated in rats with EMs, all of which were reversed upon TMP treatment. Additionally, the activities of SOD, GSH, and CAT were lowered in rats with EMs, which were partly abrogated by TMP treatment. Furthermore, the downregulation of Nrf2 and HO-1 was counteracted by TMP treatment. To sum up, TMP represses excessive oxidative stress, NLRP3 inflammasome activation, and pyroptosis in rats with EMs. Additionally, TMP may activate the Nrf2/HO-1 pathway.