Neglected and underutilized plant species (NUS) can contribute to food security, poverty alleviation, agrodiversity conservation and climate resilience in Sub-Saharan Africa (SSA). One avenue for realizing NUS’ potential is by making them components of smallholder diversification strategies. However, we lack clear evidence about how NUS are actually integrated into smallholder diversification strategies and the mechanisms through which NUS intersect with other livelihood diversification elements to affect household food security and livelihoods. We explore the interface of NUS, diversification strategies and food security using primary data from household surveys (n = 268) in Senegal through a mixed method approach combining network analysis, perception analysis, clustering analysis and structural equation modelling. Diverse NUS are collected from the wild and/or cultivated on farms, and are combined in various ways with other crop and livestock species (network analysis). Although all NUS have favorable diet-related characteristics, they are significant food and income sources only during collection/harvesting periods that, for some NUS, coincide with the lean period (perception analysis). We identify three very distinct ways through which NUS are integrated in household livelihoods and diversification strategies (clustering analysis). NUS diversity can contribute to food availability and income generation, but only the latter pathway is associated with significant positive food security outcomes (structural equation modelling). Overall, NUS are promising elements of smallholder diversification strategies, but their integration and outcomes varies substantially even within relatively confined geographical areas. Harnessing this differentiated potential can better inform NUS-related efforts to enhance household food security and agricultural resilience and sustainability in SSA.