<p>Using by-products has emerged as a critical strategy to reduce environmental impact and create value from waste. This study aimed to analyze the effect of thermal and ultrasonic pretreatments on candelilla by-products. A proximal chemical analysis of candelilla plants and by-products from three regions SJZ (San Jerónimo, Melchor Ocampo, Zacatecas), ELC (Estanque de León, Cuatro Ciénegas, Coahuila), and TD (Tlahualilo de Zaragoza, Durango) was conducted after applying pretreatments to determine the percentages of their main components. Functional group characterization was performed using FTIR, crystallinity was assessed by XRD and thermal properties were examined using DSC. Candelilla by-products retained a chemical composition rich in cellulose, hemicellulose, and lignin, even after thermal and ultrasonic pretreatments. Antioxidants from the plants and by-products were extracted and analyzed using spectrophotometric techniques. The quantification of bioactive compounds was carried out with UPLC-PDA-ESI-QqQ, revealing that SJZ and TD by-products pre-treated with ultrasound for 15 and 30&#xa0;min exhibited the highest concentration and specific phenolic compounds, dominating by region: Quercetin glucuronide in SJZ, Shikimic acid in ELC, and Ellagic acid rhamnoside in TD. In the FRAP assay, the ELC-U15 sample showed the highest antioxidant capacity (171.03 mE of gallic acid). In contrast, in the ABTS^·+ assay, the ELC-U30 sample required the lowest concentration to inhibit the ABTS^·+ radical (83.21&#xa0;µg Trolox/mL). Therefore, combining candelilla by-products with ultrasound as a pretreatment proved to be an innovative and effective strategy for phenolic compound extraction, aligned with the principles of the circular economy.</p> Graphical Abstract <p></p>