The aim of this study was to evaluate whether the addition of strawberry by-products (pulp and achene) and thermosonication offers a nectar with a potential contribution of health and safety benefits. Strawberry nectar with 0, 10 and 20% of strawberry by-products (SB) was subjected to thermosonication (24 kHz) at 70 and 80% for 8 min at 50 °C. Total soluble solids, pH, polyphenol oxidase (PO) and pectin methylesterase (PME) activities, total soluble phenols (TSP), ascorbic acid (AA), anthocyanins and antioxidant capacity (AOX) were evaluated. Microbiological reduction and inactivation of Escherichia coli was also determined. A limited activity was observed in PO and PME related to the SB percentage added. TSP, AA, anthocyanins, and AOX were increased due to the different percentages of SB added to the nectar. A reduction of aerobic mesophiles (1.28 Log CFU/mL), molds and yeast counts (1.23 Log CFU/mL) were achieved by thermosonication. E. coli inactivation was approximately 1 log CFU/mL in 20% SB nectar at 80% amplitude, 8 min at 50 °C, but increased during storage at 6 °C (0.915-5.86 Log CFU/mL). Thermosonication showed the possibility of employing strawberry by-products in nectars, improving the use of agro-industrial residues by non-thermal technologies.