This study explores the unexploited potential of Artificial Neural Network (ANN) optimization techniques in enhancing different drying methods and their influence on the characteristics of various sweet potato varieties. Focusing on the intricate interplay between drying methods and the unique characteristics of white, pink, orange, and purple sweet potatoes, the presented experimental study indicates the impact of ANN-driven optimization on food-related characteristics such as color, phenols content, biological activities (antioxidant, antimicrobial, anti-hyperglycemic, and anti-inflammatory), chemical, and mineral contents. The results unveil significant variations in drying method efficacy across different sweet potato types, underscoring the need for tailored optimization strategies. Specifically, purple sweet potatoes emerge as robust carriers of phenolic compounds, showcasing superior antioxidant activities. Furthermore, this study reveals the optimized parameters of dried sweet potato, such as total phenols content of 1677.76 mg/100 g and anti-inflammatory activity of 8.93%, anti-hyperglycemic activity of 24.42%. The upgraded antioxidant capability is presented through DPPH●, ABTS●+, RP, and SoA assays with values of 1500.56, 10,083.37, 3130.81, and 22,753.97 μg TE/100 g, respectively. Additionally, the moisture content in the lyophilized sample reached a minimum of 2.97%, holding favorable chemical and mineral contents. The utilization of ANN optimization proves instrumental in interpreting complex interactions and unlocking efficiencies in sweet potato drying processes, thereby contributing valuable insights to food science and technology.