Indapamide is an effective and safe antihypertensive medication showing a beneficial effect in combination with other antihypertensive agents regarding morbidity and mortality. A comparative study was performed under fasting and fed conditions to investigate the effect of food and selected single nucleotide polymorphisms in the uridine diphosphate glucuronyl transferase (UGT2B7) gene on the pharmacokinetics and pharmacodynamics behavior of indapamide 1.5 mg sustained release. Forty-nine healthy volunteers aged 18–55 years were randomized into two groups; 25 volunteers were administered indapamide under fasting conditions and 24 under fed conditions. Genotyping of theUGT2B7 rs7438135andrs11740316was done before commencing the study using predesigned TaqMan assays. Results showed that food independently decreased the value of indapamide’ Tmaxby 5.5 h and increased the value of Cmaxby 8.7 ng/mL. On the other hand, all genetic variants of bothUGT2B7SNPs had no significant impact on the values of Tmax, Cmax, and AUC0–t; however, it was found that rs11740316 variantAGwas correlated with a 2.8 h lower MRTinf. Finally, BMI positively correlated with longer MRTinf. It was concluded that none ofrs7438135,rs11740316, or food had a significant impact on the pharmacodynamic properties. Food had a modest impact on indapamide Cmaxand Tmaxvalues, while there were unremarkable differences in safety and efficacy.