The objective of this work was to evaluate the effect of phloretin on growth performance, serum biochemical parameters, antioxidant profile, glutathione (
GSH
)-related enzymes, nuclear factor erythroid 2–related 2 (
Nrf2
) and heat shock protein 70 (
HSP70
) in heat-stressed broilers. A total of 240, 22-day-old Arbor Acres broilers were divided into 4 groups. The control group was housed at 23.0 ± 0.61°C and fed with basal diet, while the 3 heat-stressed groups (A, B, and C groups) were housed at 30.5 ± 0.69°C and fed with basal diet containing 0, 100, and 200 mg/kg phloretin, respectively. Serum was taken form 42-day-old broilers. Results showed that heat stress decreased (
P <
0.05) the final body weight (
FBW
), body weight gain (
BWG
), feed intake (
FI
), serum total protein (
TP
), triglyceride (
TG
), triiodothyronine (T3), thyroxine (
T4
), GSH, catalase (
CAT
), and total antioxidant capacity (
T-AOC
) levels, but increased (
P <
0.05) the feed-to-gain ratio (
FGR
) and serum malondialdehyde (
MDA
) levels in broilers compared with that in the control group. Among the heat-stressed groups, supplementary 200 mg/kg phloretin increased (
P <
0.05) the FBW, BWG, FI, serum TP, TG, T4, GSH, CAT, and T-AOC levels, and decreased (
P <
0.05) the FGR and serum MDA in broilers. There were significant decreases (
P <
0.05) in the glutathione peroxidase (
GSH-Px
), γ-glutamylcysteine synthetase (
γ-GCS
), and Nrf2, but significant increases (
P <
0.05) in the HSP70 of the broiler serum after heat stress treatment. Among the heat-stressed groups, supplementary 200 mg/kg phloretin increased (
P <
0.05) the GSH-Px, γ-GCS, and Nrf2 levels, but decreased (
P <
0.05) the serum HSP70 level in the heat-stressed broilers. Under high temperature condition, FBW, BWG, FI, FGR, serum TP, TG, T4, MDA, GSH, CAT, T-AOC, GSH-Px, γ-GCS, Nrf2 and HSP70 were linearly affected by inclusion of phloretin. These results indicated that phloretin may improve growth performance, serum parameters, and antioxidant profiles through regulated GSH-related enzymes, Nrf2 and HSP70 in heat-stressed broilers.