Although spice extracts are well known to exhibit antibacterial properties, there is lack of a comprehensive evaluation of the antibacterial effect of spices against antibiotic-resistant bacteria. In the present study, ethanolic extracts from a total of 67 spices were comprehensively investigated for their in vitro antibacterial activities by agar well diffusion against two common food-borne bacteria, Staphylococcus aureus and Salmonella enteritidis, with multi-drug resistance. Results showed that S. aureus was generally more sensitive to spice extracts than S. enteritidis. Of the 67 spice extracts, 38 exhibited antibacterial activity against drug-resistant S. aureus, while only four samples were effective on drug-resistant S. enteritidis. In addition, 11 spice extracts with inhibition zones greater than 15 mm were further verified for their broad-spectrum antibacterial properties using another 10 drug-resistant S. aureus strains. It was found that five spice extracts, including galangal, fructus galangae, cinnamon, yellow mustard seed, and rosemary, exhibited the highest antibacterial capacity. Further cytotoxicity of these 11 spices was determined and LC50 values were found to be more than 100 μg/mL except for galangal, rosemary, and sage, whose LC50 values were 9.32 ± 0.83, 19.77 ± 2.17, and 50.54 ± 2.57, respectively. Moreover, the antioxidant activities (ferric-reducing antioxidant power (FRAP) and trolox equivalent antioxidant capacity (TEAC) values) and total phenolic content (TPC) of spice extracts were determined to establish possible correlations with the antibacterial activity. Although the antibacterial effect was positively correlated with the antioxidant activities and TPC, the correlation was weak (r < 0.5), indicating that the antibacterial activity could also be attributed to other components besides antioxidant polyphenols in the tested spice extracts. In conclusion, dietary spices are good natural sources of antibacterial agents to fight against antibiotic-resistant bacteria, with potential applications as natural food preservatives and natural alternatives to antibiotics in animal feeding.