Misoprostol, a prostaglandin E1 analog, is widely used in obstetrics for abortion induction and labor management. Although generally safe, it can lead to rare complications such as uterine rupture, even in patients without prior uterine scarring. This case report describes a 27-year-old gravida 3, para 1 woman with no history of uterine surgery who presented with a second-trimester missed septic abortion. After receiving six sublingual doses of misoprostol (400 μg each) without fetal expulsion, she developed signs of sepsis, including fever, tachycardia, and leukocytosis. Ultrasound revealed an empty uterus with a defect in the anterior wall and the fetus and placenta in the peritoneal cavity. Emergency laparotomy confirmed a complete transverse rupture of the lower uterine segment with necrotic edges. The fetus and placenta were extracted, the uterus was repaired, and the patient recovered well with postoperative antibiotics, being discharged after 7 days. This case highlights uterine rupture as a rare but serious complication of second-trimester abortion with misoprostol, emphasizing the importance of careful monitoring and prompt recognition of complications to ensure patient safety.