Background: Functional, behavioral, and cognitive disabilities often contribute to the difficulties in rehabilitation programs of victims with post-craniotomy. Aim: Determine the effect of the pre rehabilitation program on cognitive and motor functions for patients post-craniotomy. Subjects and Methods: Quasi-experimental research design was used. Setting: This study was carried out at the neurosurgery department and neurosurgery outpatients' clinic at Mansoura University Hospital. A convenient sample of 70 oriented patients post craniotomy was classified into the study (who received a rehabilitation program and the control group (35 in each group). Tools: (I) Patients' assessment sheet post craniotomy, Tool (II): Patients' knowledge, regarding craniotomy (pre and post-test), Tool (III): Patients' reporting practice regarding post craniotomy exercise (IV) Mini–mental state examination (MMSE), and (V) Berg balance scale(PBS). Results: In comparison to patients in the control group, participants in the pre-rehabilitation group showed a statistically significant increase in their knowledge, practice, motor, and cognitive abilities following pre rehabilitation programme (p. value < 0.01). Conclusion: When a pre-rehabilitation program is implemented, patients' knowledge, practice, and motor and cognitive abilities after a craniotomy significantly improve. Recommendation: All patients who have had a craniotomy should participate in a pre-rehabilitation program.