Nickel‐doped mesoporous carbon (MC) materials with 1, 4, and 7 wt. % nickel/MC, were synthesized and utilized for the elimination of indole, as representative of nitrogen‐containing compounds, from a model diesel fuel. Different instrumental techniques, including Fourier‐transform infrared (FT‐IR) spectroscopy, X‐Ray diffraction (XRD), N2 adsorption‐desorption analyses, field emission scanning electron microscopy (FE‐SEM), energy‐dispersive X‐ray spectroscopy (EDXS), and transmission electron microscopy (TEM) were used to characterize the synthesized Ni‐doped mesoporous carbons. The XRD and N2 adsorption‐desorption results revealed that all the nickel‐modified materials had ordered hexagonal mesostructures. Response surface methodology coupled with a three‐variable, three‐level Box‐Behnken design (BBD) involving three center points and one response was employed for evaluating the influence of the three input parameters, namely temperature (A), contact time (B), and Ni content (C) on the adsorption yield. The optimum removal efficiency (96.5 %) was obtained at 42 °C, 1 wt. % of Ni loading, and 55 min contact time; also, possible adsorption mechanisms might be due to van der Waals interaction, H‐bonding, and π‐complexation. Additionally, the equilibrium data were analyzed using Langmuir, Freundlich, and Temkin isotherm models, and the Freundlich isotherm model showed a better fit to experimental data (R2 =0.9978).