Abstract The conversion of vanillin from biomass is an important sustainable practice, enabling the generation of valuable products from renewable resources. This study considered the aldol condensation of vanillin with acetone using conventional heating and microwave irradiation, catalyzed by hydrotalcite‐type materials. These catalysts were synthesized via a combined mechanochemical coprecipitation method to reduce synthesis time and waste. Variables such as molar metal ratio and isomorphic substitution in hydrotalcite with nickel species were explored. The results show that hydrotalcites are efficient catalysts for the aldol condensation of vanillin, achieving conversion rates of 60% to 90% within 120 min under microwave irradiation. This approach aligns with green chemistry principles, offering high selectivity and rapid reaction times, and highlighting the efficiency of hydrotalcites in catalytic applications.