In this study, highly fluorescent sulfur and nitrogen doped carbon quantum dots (S,N-CQDs) were used as fluorescent nanosensors for direct spectrofluorimetric estimation of each of gliclazide (GLZ) and saxagliptin (SXG) without any pre-derivatization steps for the first time. S,N-CQDs were synthesized employing a simple hydrothermal technique using citric acid and thiosemicarbazide. The produced S,N-CQDs were characterized using different techniques including fluorescence emission spectroscopy, UV spectrophotometry, high-resolution transmission electron microscopy and FT-IR spectroscopy. Following excitation at 360 nm, S,N-CQDs exhibited a strong emission peak at 430 nm. The native fluorescence of S,N-CQDs was quantitatively enhanced by addition of increased concentrations of the studied drugs. The fluorescence enhancement of S,N-CQDs and the concentrations of the studied drugs revealed a wide linear relationship in the range of 30.0–500.0 µM and 75.0–600.0 µM with limits of detection of 5.0 and 10.15 µM for GLZ and SXG, respectively. The proposed method was efficiently used for determination of cited drugs in their commercial tablets with % recoveries ranging from 98.6% to 101.2% and low % relative standard deviation values (less than 2%). The mechanism of interaction between S,N-CQDs and the two drugs was studied. Validation of the proposed method was carried out in accordance with International Conference on Harmonization (ICH) guidelines.