It is estimated that 45 million people suffer from schizophrenia around the world; it is among the top ten leading causes of disability. By 2050, this number will have grown to approximately 71 million people. Mental illnesses contribute more to the global burden of disease than all cancers combined. The present study has been planned to evaluate the effect of anticholinergic parkinol (benzhexol hydrochloride) and akineton (biperiden hydrochloride) on erythrocyte acetyl cholinesterase (AChE) activity and serum activities of gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in schizophrenic patients treated with haloperidol, and also to study the effect of the previously mentioned two anticholinergics on both the cognitive functions and psychiatric symptoms in such patients. The study was carried out on 30 male schizophrenic patients who were divided into two main groups (group 1 and group 2) each of 15 patients of comparable age. The present results revealed that the total score of (PANSS) showed a significant decrease in all studied groups. The total score of (MMSE) showed a significant increase in all studied groups. The AChE activity did not show any significant difference in all comparisons in all studied groups. In our study, there was a significant elevation of serum GGT, ALT, AST and ALP levels in some groups of treated patients as compared to pretreatment groups. The results obtained in our study showed a significant increase in serum GGT, ALT, AST, and ALP levels in groups treated with either (haloperidol+benzhexol hydrochloride) or (haloperidol+biperiden hydrochloride) as compared to the corresponding levels in groups treated with haloperidol only, respectively. From all results we can concluded that the biochemical parameters used in this study are useful in detecting any side effects of antipsychotic and anticholinergic drugs on liver functions. The treatment with (haloperidol+benzhexol hydrochloride) and (haloperidol+biperiden hydrochloride) are effective in decreasing the positive and negative symptoms of schizophrenia.