The electrochemical ethanol oxidation reaction (EOR) plays a crucial role in electrochemical hydrogen production and direct ethanol fuel cells, both vital for utilizing renewable energies. Ni-based catalysts are pivotal in enabling efficient EOR, leading to the formation of acetic acid/acetaldehyde or CO2. These can serve as alternative anodic oxidation reactions for oxygen evolution reaction (OER) in water electrolysis or the anodic reaction for direct ethanol fuel cells, respectively. This review explores recent advancements in EOR over Ni-based catalysts. It begins with an overview of EOR performance across various Ni-based catalysts, followed by an examination of the reaction chemistry, mechanism, and active sites. The review then delves into strategies for designing highly active Ni-based EOR catalysts. These strategies include promotion with transition metals, noble metals, nonmetals, and carbon materials, as well as creating amorphous structures, special morphologies, and single-atom catalysts. Additionally, it discusses the concept of self-supporting catalysts using three-dimensional porous substrates. Finally, the review highlights emerging methodologies that warrant further exploration, along with future directions for designing highly active and stable EOR catalysts.