Background <p>Propofol is widely used for sedation during gastrointestinal endoscopy and is generally considered safe for patients with epilepsy. However, a tiny subset of patients may experience seizure-like phenomena (SLP) following its administration.</p> Case description <p>We present a case of a 28-year-old woman who experienced SLP on two separate occasions after propofol administration during gastroscopy and colonoscopy. The patient developed generalized tonic-clonic seizures after receiving propofol, requiring emergency management with midazolam. All preoperative examinations, including electroencephalogram and head CT, showed no abnormalities. On the third endoscopic procedure, remimazolam was used instead of propofol, resulting in the successful completion of the procedure without any adverse events.</p> Comments/review <p>Propofol exhibits complex neuropharmacology capable of inducing paradoxical excitation through multiple interconnected mechanisms. Evidence points to transient neural instability during rapid concentration shifts in induction and emergence phases, altered brain network dynamics, individual genetic susceptibility in calcium homeostasis, and potential glycine receptor antagonism as contributing factors to SLP. In this context, remimazolam presents a mechanistically rational alternative due to its selective GABAergic activity without paradoxical excitation, inherent anticonvulsant properties, and enhanced safety profile including flumazenil reversibility. This review consolidates current evidence establishing remimazolam as a safe and effective sedative alternative for patients with documented propofol-induced SLP</p> Conclusions <p>This case highlights the potential for propofol to induce SLP even in patients without underlying neurological disorders. Remimazolam appears to be a safe and effective alternative for patients who experience propofol-related SLP during procedural sedation.</p>