Layered Double Hydroxides (LDHs), a class of anionic clays have garnered significant attention as a potential electrochemical active material. Due to their unique properties such as high surface area, high electrical conductivity, improved active sites, and tunable capability, they have been extensively used in the field of electrochemical sensors. On the other hand, nilutamide (NLD) is an anti-androgen drug used for the treatment of prostate cancer. However, excessive usage can lead to severe effects, thus making it essential for sensitive and selective NLD detection in the environment. Herein, we have prepared nickel aluminum (NiAl) LDH as an efficient electrode material for the electrochemical detection of nilutamide (NLD). The NiAl-LDH was obtained by a simple coprecipitation method. The physicochemical analysis was carried out using various analytical techniques including XRD, FT-IR, XPS, and Raman, which confirmed its successful formation. Further, FESEM and TEM analysis of NiAl-LDH were exhibited to prove the topological structures of the as-prepared material. The glassy carbon electrode was modified with the prepared NiAl-LDH and its electrochemical performance was studied with cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The modified NiAl-LDH/GCE displayed excellent electrocatalytic activity towards the reduction of NLD at −0.55 V with a wide linear range of 0.029–1543.8 μM. It also exhibits a lower detection limit of 0.005 μM with a sensitivity of 15.64 μA μM−1 cm−2. Moreover, other potential interfering compounds showed no interference effect on NLD sensing. Also, the detection of NLD in spiked river water samples verified the fabricated electrode’s real-time applicability.