Previously developed fluorophenyl-isoxazole-carboxamides derivatives were re-synthesized and their scavenging activity against DPPH free radical and inhibitory activity against lipase and α-amylase enzymes were evaluated. The inhibition of the tested enzymes was weak while the most potent activities were observed in the DPPH assay. In particular, compounds 2a and 2c demonstrated high antioxidant potency with IC50 values of 0.45 ± 0.21 and 0.47 ± 0.33 µg/ml, respectively, when compared to Trolox, the positive control compound, which has an IC50 value of 3.10 ± 0.92 µg/ml. Based on the in vitro results, the most potent compound 2a was chosen for in vivo evaluation of antioxidant properties using 20 male mice injected intra-peritoneally and divided into four groups. The in vivo results revealed that total antioxidant capacity (TAC) obtained for mice treated with 2a was two folds greater than that of mice treated with the positive control Quercetin. Although further biological and preclinical investigations need to be performed to assess the therapeutic potential of 2a, the results of this study show promising antioxidant activities both in vitro and in vivo.