Spices have long been used to improve food flavor, due to their appealing fragrance and sensory attributes. Nowadays, spices-based bioactives, particularly phenolic compounds, have gained attention due to their wide range of significant effects in biological systems. The present study was conducted to characterize the 12 widely used spices (allspice, black cardamom, black cumin, black pepper, cardamom, cinnamon, clove, cumin, fennel, nutmeg, star-anise, and turmeric) for their phenolics with the liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS2), polyphenols estimation, and their antioxidant potential. Total phenolics, total flavonoids, and total tannin content and their antioxidant activities were estimated in all spices. Clove and allspice had the highest value of total polyphenol content (215.14 and 40.49 mg gallic acid equivalent (GAE) per g of sample), while clove and turmeric had the highest total flavonoids (5.59 mg quercetin equivalent (QE) per g of sample) and total tannin contents (23.58 mg catechin equivalent (CE) per g of sample), respectively. On the other hand, black cumin and black pepper had the highest phosphomolybdate activity (15.61 and 15.43 mg ascorbic acid equivalent (AAE) per g of sample), while clove was almost identified with highest free radical scavenging capacity. A positive correlation was observed among phenolic compounds and antioxidant activities. In this quest, a total of 79 phenolic compounds were tentatively characterized by using LC-ESI-QTOF-MS2 including 26 phenolic acids, 33 flavonoids, 16 other polyphenols, and 4 lignans. The high-performance liquid chromatography coupled with photodiode array detector (HPLC-PDA) quantification of phenolic compounds exhibited higher phenolic acids. These results provided us some valuable information that spices have powerful antioxidant potential that can be further used in human food and animal feed as a supplement for different health promoting applications.