This study aimed to assess the current water quality status across various regions within the Fayoum depression by examining water canals, drains, and potential contaminants impacting public health and the local ecosystem. Additionally, an adsorption treatability investigation was conducted on various antibiotics identified during the assessment. Fifteen sampling points were selected across the Fayoum depression, covering surface water bodies and agricultural drainage systems during both winter and summer seasons. Physico-chemical, microbiological, and antibiotic analyses were performed on collected water samples. The water quality parameters investigated included pH, electrical conductivity, total dissolved solids (TDS), total coliforms, fecal coliforms, and concentrations of antibiotics such as ciprofloxacin and tetracycline. The findings revealed significant variations in water quality parameters among different water sources, categorizing them into three types: irrigation canals, polluted canals, and drains. High contamination levels were observed in certain water canals and drains due to untreated sewage and agricultural drainage discharge. Notably, elevated TDS levels (exceeding 1200 mg/L), microbial indicators count (with total coliforms reaching up to 2.3 × 106 CFU/100 mL), and antibiotics (with concentrations of ciprofloxacin and tetracycline exceeding 4.6 µg/L) were detected. To mitigate antibiotic contamination, a Phyto-adsorption treatability study using magnetite nanoparticles prepared with Phragmites australis plant extract demonstrated promising results, achieving complete removal of high antibiotic concentrations with an adsorption capacity of up to 67 mg/g. This study provides updated insights into water quality in the Fayoum depression and proposes a novel approach for addressing antibiotic contamination, potentially safeguarding human and environmental health.