The present study investigated the effects of
Lactobacillus acidophilus
(LBA) and mannan-oligosaccharides (MOS) supplementation on the production performance, serum biochemistry, antioxidant profile, health indices, meat quality, and lipid oxidative stability of broiler chicken. A total of 252 commercial broiler chickens at 1 d old of uniform body weight were randomly allocated to 6 maize-soybean-based dietary treatments: T
1
(control diet), T
2
( antibiotic bacitracin methylene di-salicylate [BMD] at 20 mg/kg diet), T
3
(MOS at 0.1% + LBA at 10
6
CFU/g feed), T
4
(MOS at 0.1% + LBA at 10
7
CFU/g feed), T
5
(MOS at 0.2% + LBA at 10
6
CFU/g feed), and T
6
(MOS at 0.2% + LBA at 10
7
CFU/g feed). Each treatment was assigned to 6 replicates of 7 birds. The samples for meat quality and serum biochemistry analysis were taken from 12 birds per treatment (2 birds/replicate). The results revealed better (
P <
0.01) growth performance and production efficiency of birds fed either T
5
or T
6
diet compared to control or BMD supplemented diet and BMD-supplemented birds superseded the control birds. Higher (
P <
0.01) serum and liver antioxidant enzyme activities, meat antioxidant capacity (2, 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid [ABTS] and 1, 1-diphenyl-2-picrylhydrazyl [DPPH] assays], serum total protein, high-density lipoproteins (HDL) cholesterol (
P <
0.05), and globulin levels (
P <
0.01) were observed in birds fed either T
5
or T
6
diet compared to control or BMD supplemented birds, whereas, lower lipid oxidation (
P <
0.01), cardiac risk ratio, atherogenic coefficient, atherogenic index of plasma, serum glucose, triglyceride, total cholesterol levels (
P <
0.01), and serum albumin-to-globulin ratio (
P <
0.05) were observed in the chickens. The pH of meat from birds fed T
4
, T
5
or T
6
diet was lower (
P <
0.01) compared to control and other treatments. The extract release volume (ERV), water holding capacity (WHC), and protein content of meat were higher (
P <
0.05) in birds fed either T
5
or T
6
diet compared to control or BMD supplemented birds. Thus, it was concluded that the supplementation of 0.2% MOS along with LBA at 10
6
CFU/g is optimum for better growth performance, serum biochemistry, antioxidant profile, health indices, meat quality, and lipid oxidative stability of broiler chickens.