Chronic inflammatory conditions such as obesity, type-2 diabetes, and cardiovascular diseases are the leading causes of mortality worldwide. Hence, much research interest in bioactive peptides has been stimulated due to lack of potent pharmacological interventions. Although many such peptides have been identified from food proteins, insufficient information is available on their structure-function relationship. Presence of hydrophobic and positively charged amino acids is a common occurrence for the peptides with anti-inflammatory properties. However, inconsistent findings have also been reported. Most of the food-derived peptides exhibited their anti-inflammatory activities primarily by inhibiting signaling components of either NF-κB or MAPK pathway, which are the two major pathways involved in chronic inflammation following uncontrolled signal activation. This review highlighted the structural requirements of the peptides to exhibit anti-inflammatory activity based on the current knowledge about food-derived anti-inflammatory peptides and their underlying molecular mechanisms of action. PRACTICAL APPLICATIONS: While research in the food-derived bioactive peptide is gaining momentum, but the ability to translate these new findings into the commercial product such as nutraceuticals and functional foods, remains delayed. The most prominent reasons for this delay are the lack of detailed research on, (i) the structure-function relationship of the peptide and the underlying molecular mechanisms of these bioactive peptides, and (ii) the interaction of these peptides with different cellular elements in the disease pathophysiology. This review gives an insight into the structure-activity relationship of bioactive peptides involved in anti-inflammatory responses. The information provided here would be highly beneficial to describe the possible anti-inflammatory activity of any newly identified peptides from different food sources.