This study explores three methods to enhance the quality of Ghanaian garlic before drying: basic ultrasound [sonication (US)], ultrasound with a soaking solution [osmosonication (US + OD)], and vacuum with ultrasound and soaking [vacuum-assisted osmosonication (V + US + OD)]. We looked at how these methods affect garlic’s antioxidants, phenolic and flavonoid content, enzyme activity, rehydration, drying time, energy use, and chemical makeup. The vacuum with ultrasound and soaking method was the best, improving most quality measures, shortening drying time, and saving energy. This method also preserved the garlic’s chemical integrity and had the highest allicin content. Overall, the results ranked the methods as V + US + OD > US + OD > US.