Nicked-based metal−organic framework-derived carbon (Ni/MOFDC) and its acid-treated counterpart (AT-Ni/ MOFDC) have been prepared as supports for palladium nanoparticle electrocatalysts (Pd/Ni/MOFDC and Pd/AT-Ni/MOFDC). These materials have been prepared using facile microwave-assisted techniques. Several spectroscopic and microscopic techniques (such as FTIR, Raman, PXRD, XPS, XANES, FT-EXAFS, and TEM) have been used to thoroughly characterize physicochemical properties of the materials. It is revealed that acid treatment successfully cleaned the metallic Ni surface of the passivating hydroxides (Ni(OH) 2 and NiOOH) to generate a very low concentration of Ni nanoparticles on the carbon support. The Ni-deficient Pd/AT-Ni/MOFDC shows excellent electrocatalytic performance toward ethanol oxidation reaction (EOR) in the alkaline medium compared to the Ni-hydroxide-rich Pd/Ni/MOFDC counterpart.As a proof-of-concept, these electrocatalysts have been employed as anodes and demonstrated for membraneless direct ethanol microfuel cells (μ-DEFCs) with a micro-3D-printed cell, with FeCo/C as electrocatalyst for the oxygen reduction reaction at the cathode. The Pd/AT-Ni/MOFDC displays increased peak power density (P m = 26.49 mW cm −2 ) with 68% voltage retention after a 24 h galvanostatic discharge test at 40 mA cm −2 and reduced impedance. The improved electrocatalytic properties of the Pd/AT-Ni/MOFDC underscore the need to clean the nickel surface of its passivating hydroxides to harness its full promotional activities toward alcohol oxidation reaction on precious metal electrocatalysts.