Background: Drug overdose poisoning is a common cause admission at medical emergency unite. With chief complaint resulting many complications as central nervous system, hypothermia, respiratory depression, hypotension. Aim of the study: This study was carried out to evaluate the effect of Implementing Nursing guidelines regarding drug overdose poisoning among critically ill patients at Medical Emergency Unite at Assiut University Hospitals. Subjects and Methods: Research design: a quasi-experimental design. Setting: Medical emergency unite at Assiut University Hospitals and the study started from July 2016 till July 2018. Subjects: A convenience sample of 60 adults' critically ill patients diagnosed with drug overdose poisoning. The patients were assigned into two equal groups (control and study group).Tools: two tools were utilized to collect data, Tool I: Patient's assessment questioner that consists of three parts: part one: assessment of the Patients profile, part two: drug overdose data questioner, part three: biomedical data and level of conscious. Tool II: patients outcomes questioner that consist of part one: Laboratory tests findings, part two: hospital stay and progress part three: complications of poisoning) Methods: The research done from first day of admission for twenty four hours and every shift during this phase the patients received the nursing guidelines, this was done by comparing the results of outcomes for the both groups by using tool two. Results: (34%-26.7%) from age groups (30-40) years in the both groups. The highest percentage of the two groups ( 36.7% and 50%) were males. There was hypotension in control group with means of (95±11.37- 59.2±6.47) respectively. But in study group, normal with mean (99.9±10.28- 65.63±5.86 ) respectively. There were highly statistical significant differences between both groups with p value = (0.005**). ( 36.3 -30%) in the both groups had experienced metabolic acidosis Conclusion: The study group who implemented nursing guidelines was found to experience lesser complications than control group. Recommendations: Developing management and apply clinical practice guidelines for optimal patient care with drug overdose poisoning.