Developing rapid analytical methods for bioactive components and predicting both the concentration and biological availability of nutraceutical components in foods is a topic of growing interest. Here, analysis of bioactive components and total antioxidant activity in food matrices using infrared spectroscopy coupled with chemometric predictive models is described. Infrared spectroscopy offers an alternative to wet chemistry, chromatographic determination of antioxidants, and in vitro biochemical assays for assessment of antioxidant activity. Spectroscopic methods provide a technique that can be used with biological tissues without extraction, which can often lead to degradation of the antioxidant components. Sample preparation time greatly decreases and analysis time is very short once a predictive model has been developed. Spectroscopic methods can have a high degree of precision when applied to analysis of nutraceutical compound concentration and antioxidant activity in foods. This article summarizes recent advances in vibrational spectroscopy and chemometrics and applications of these methods for antioxidant detection in foods.