Tricyclic antidepressants are a class of antidepressants, an overdose of which may cause anticholinergic syndromes. In severe cases, fatal central nervous system failure and cardiovascular toxicity may occur. This case report describes a middle-aged female patient who was suffered from unconsciousness, respiratory failure, and recurrent seizures due to tricyclic antidepressant toxicity. Emergent endotracheal intubation and sedative drug treatment were failed to improve her condition. Given the absence of typical anticholinergic symptoms, the diagnosis was established followed by a 12-lead electrocardiogram examination and a series of toxic-drug screening. The patient received treatments with sodium bicarbonate, anti-epileptic drugs, and vasopressor support, which led to full recovery from the intoxication. The authors expect that by sharing this case and introducing the clinical symptoms, diagnosis, and treatment of tricyclic antidepressant-induced toxicity, clinicians could be more familiar with this syndromes. We would like to remind our peers that in clinical settings, patients presenting with drug overdose often took several drugs concomitantly. As such, the toxic syndrome is often atypical which increases the difficulty of clinical diagnosis. The combination of medical history inquiry, physical examination, and laboratory tests remains the key for diagnosing drug toxicity at the early stage.