In this work, we report the development of highly fluorescent materials for the selective and sensitive detection of ibuprofen (IBP). Novel nonionic alginate polymers and their CdTe quantum dots (QDs) were synthesized and characterized using FT-IR, 1H NMR, TEM, UV–vis, and EDAX techniques. The nonionic alginate-capped CdTe QDs show tremendously enhanced fluorescence intensity (∼30 times), increased quantum yields up to 49% (∼10 times), and improved biocompatibility (IC50 = 1414 μg mL−1) compared with that of pristine CdTe QDs. The synthesized CdTe QD-Al-PEG2000(SH)2 was successfully used as an optical sensor to detect IBP based on multiple hydrogen bonding interactions between the sensor and IBP. The quenching effect on the fluorescence intensity of the sensor showed very good linearity in the range 1.0–30 μmol L−1 (R2 = 0.9959) and a remarkably low detection limit of 0.004 μmol L−1, (S/N = 3). The sensor was highly selective to IBP in the presence of other potentially competing compounds and was successfully applied for the detection of IBP in urine and human serum samples with good recoveries. This reported method is expected to open new possibilities for the cost-effective, non-toxic, selective, and highly sensitive optosensing of IBP.