Several cognitive domains show decline with increasing age, which is associated with poorer work performance and reduced quality of life. As many nations show a rise in the number of citizens aged over 60 years, the study of the mechanisms underlying age-related cognitive functional reductions, such as inflammation, is important. Inflammaging has been implicated in progressive minor decline through to dementia typologies, with peripheral cytokine patterns investigated for their potential role in cognitive function. Assessing the relationship between these markers and cognitive performance could elucidate mechanisms with aging beyond neuropathologies. The research literature suggests peripheral cytokines/chemokines such as interleukin-6 and c-reactive protein are associated with cognitive processing. In this systematic review, we examine the evidence for a relationship between a range of peripheral inflammatory markers and domains of cognitive function in healthy older adults. To do this, a literature search was conducted using the following databases: SCOPUS, PubMed, Web of Science, and PsycINFO. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Twenty-nine studies met our inclusion criteria. Although a wide range of systemic inflammatory biomarkers were examined, IL-6 and CRP were the most studied. The evidence suggests an inverse inflammatory biomarker-cognitive function relationship whereby elevations in most cytokines were associated with poorer performance across cognitive domains. The findings contribute to our understanding of peripheral inflammation and domains of cognitive function, offering insight into inflammaging processes.