Background: Drug addiction is major societal problem all over the world that associated with acute kidney injury (AKI).  The impact of urinary neutrophil gelatinase-associated lipocalin (NGAL) and Calprotectin on the early diagnosis of AKI have been investigated, yet no earlier comprehensive studies had been conducted in their impact among drug abuse. Aim of the Work: This work aimed to evaluate the role of urinary NGAL and Calprotectin in predicting AKI among drug abuse intoxicated cases admitted to Poison control Center Ain Shams University Hospitals (PCCASUH). To compare the accuracy of urinary NGAL and calprotectin in the diagnosis of AKI. Materials and Methods: A prospective observational study was performed on 75 patients, who were presented to (PCCASUH) with acute drug abuse toxicity from September 2018 to March 2019. Blood and urine samples were collected from all patients on the 1^st, and 3^rd day of admission. Urine NGAL and Calprotectin were assessed and compared between patients who developed AKI and who didn't. Results: 75 patients included in the study, 20 developed AKI. At 1^st day of admission, the mean urinary NGAL and urinary calprotectin were significantly elevated among AKI group. In third day of admission there were further significant elevation. ROC curve analysis revealed that NGAL developed sensitivity of 93.0% and a specificity of 83.0% whereas urinary calprotectin developed a sensitivity of 88.4% and a specificity of 96% Conclusion and recommendations: Our findings deduced that urinaryNGAL and urinarycalprotectin levels significantly elevate in acute drug abuse intoxication cases who developed AKI for up to 72 hours of hospitalization, hence it may be regarded as an early predictors of AKI and Calprotectin could be considered more accurate. It is recommended that, all acute drug abuse intoxicated patients a urinary NGAL and Calprotectin should be done for early exclusion of AKI that could be complicating.