Nine variously substituted azo dye derivatives 2–10 of antipyrine were prepared. The effects of the nature and orientation of the substituents on the color and dyeing properties of these dyes for polyester fibers were evaluated. The newly synthesized compounds were characterized on the basis of elemental analyses and spectral data. On the other hand, the investigated dyes were applied to polyester fabrics and showed good light, washing, heat, and acid perspiration fastness. The remarkable degree of brightness after washings is indicative of the good penetration and the excellent affinity of these dyes for the fabric. The results in general revealed the efficiency of the prepared compounds as new monoazo disperse dyes. The newly synthesized compounds were screened for their antioxidant and cytotoxic activity against Vitamin C and 5-fluorouracil, respectively. The data showed clearly that most of the compounds exhibited good antioxidant and cytotoxic activities.