Objective To investigate the clinical features, characteristics under white‑light endoscopy and endoscopic ultrasonography, and treatment strategies of gastritis cystica profunda (GCP) accompanied with or without neoplastic lesions. Methods Clinical data of 35 patients, who were pathologically diagnosed as having GCP after endoscopic or surgical resection in Beijing Friendship Hospital, Capital Medical University from January 2015 to February 2021, were retrospectively collected, including 27 patients with neoplastic lesions. The demographic information, clinical manifestations, endoscopic features, treatment methods, and pathological results of GCP were summarized. Results Thirty‑five patients with GCP were 68.26±8.08 years old, and mostly male (80.00%, 28/35). The most common symptom was upper abdominal pain, accounting for 31.43% (11/35), and 25.71% (9/35) had no symptoms. Other symptoms included acid reflux, heartburn, abdominal distension, anemia, and choking sensation after eating. The most common site of GCP was cardia (51.43%, 18/35), and the main endoscopic manifestations of GCP were flat mucosal lesions (68.57%, 24/35), mainly 0‑Ⅱa and 0‑Ⅱa+Ⅱc type lesions, accounting for 66.67% (16/24). The second common endoscopic manifestation was polypoid eminence (20.00%, 7/35). Endoscopic ultrasonography was performed in 15 patients, with main manifestations of uniform hypoechoic with or without cystic echo (73.33%, 11/15). Among the GCP cases, 33 patients received endoscopic resection, and 2 received surgical treatment. The treatment processes were all successfully completed, and en‑bloc resection was accomplished for all lesions receiving endoscopy, with the mean endoscopic operation time of 86.13 min. One patient suffered postoperative delayed bleeding after ESD which was stopped by endoscopic hemostasis. Final pathological results showed that the proportion of GCP complicated with neoplastic lesions was 77.14% (27/35), 68.57% (24/35) with early gastric cancer or precursor. Twenty‑three cases achieved R0 resection. One case showed positive basal resection margin and vascular invasion, and recurrence happened in situ at the 5th month of follow‑up, surgical resection was then performed. The endoscopic complete resection rate was 95.83% (23/24). Conclusion GCP usually occurs in middle‑aged and elderly male, often located in cardia, manifested mainly as flat mucosal lesions and polypoid changes. Endoscopic ultrasonography shows a high diagnostic value for GCP, and endoscopic treatment is safe and effective minimally invasive treatment for GCP.