Anticholinergic drugs, such as biperiden, benztropine, and diphenhydramine, were used for neuroleptic malignant syndrome (NMS) in the 1980s and 1990s. However, they have not been recommended for pharmacotherapy in NMS since 2000, as they may prevent a decrease in body temperature by suppressing sweating. However, whether anticholinergic drugs actually exacerbate NMS remains unclear. This study highlights the usefulness of anticholinergic drugs, which are no longer attracting attention as current pharmacological treatments for NMS. I treated four NMS patients using anticholinergic drugs. Two patients were treated with biperiden alone, and the other two patients were treated with a combination of biperiden and other drugs, including dantrolene, amantadine, or diazepam. Intramuscular injection of biperiden improved muscle rigidity, tremors, dysphagia, and akinetic mutism. Psychiatrists are familiar with anticholinergic drugs as they are used for antipsychotic-induced akathisia and Parkinsonism. My study suggests that anticholinergic drugs, especially injectable formulations, can be a therapeutic option for NMS.