Upper gastrointestinal endoscopy (GIE) is essential for diagnosing and treating gastrointestinal disorders in children aged 6-12 years, yet it often requires sedation due to the significant discomfort and pain involved. We conducted a PRISMA 2020-compliant systematic review of randomized controlled trials (RCTs) from PubMed, Web of Science, Scopus, and Ovid (inception to March 30, 2024). Inclusion criteria are as follows: RCTs comparing sedative regimens (e.g., propofol, ketamine, remimazolam, dexmedetomidine) in children undergoing upper GIE. Exclusion criteria are as follows: non-RCTs, studies outside the age range, or non-English publications. Risk of bias was assessed using Cochrane ROB-2. Data were extracted for recovery time, hemodynamic parameters, and adverse events (hypoxia, bradycardia, dizziness). A systematic synthesis of outcomes was performed, with results presented descriptively and quantitatively (e.g., event rates, mean differences) to compare regimens. Nineteen RCTs were included with a total of 1955 patients. Propofol, either alone or in combination, was frequently used. The propofol-ketamine combination showed better hemodynamic stability (92.2 ± 16.8 bpm) compared to propofol-fentanyl (76.8 ± 13.8 bpm). S-ketamine demonstrated dose-dependent effects-0.3 mg/kg provided the shortest recovery time (33.5 min) with moderate dizziness (40.0%)-while 0.5 mg/kg offered optimal heart rate maintenance (93.81 bpm) but longer recovery (35.67 min) and increased dizziness (43.3%). The 0.7 mg/kg dose showed faster recovery than 0.5 mg/kg (33.5 vs 35.67 min), but the highest dizziness rates (73.3%). Post-procedural complications were minimal except for dose-dependent neurological effects with S-ketamine (visual disturbances peaking at 27.6% with 0.3 mg/kg). Remimazolam showed the fastest recovery overall. Adverse events varied by regimen: propofol-ketamine had higher hypoxia (6.8%) and dizziness (34.1%), while propofol-fentanyl showed more bradycardia (24.4%). Overall, remimazolam and dexmedetomidine regimens were linked to fewer complications, though they required careful monitoring for hypotension. However, heterogeneity in outcomes (e.g., recovery times, adverse events) underscores the need for individualized regimen selection. Limitations include variability in study designs and insufficient data on minimal effective doses. Further RCTs should standardize outcome measures and optimize dosing for children undergoing endoscopy.