The parallel β-helix is a geometrically regular fold commonly found in the proteomes of bacteria, viruses, fungi, archaea, and some vertebrates. β-helix structure has been observed in monomeric units of some aggregated amyloid fibers. In contrast, soluble β-helices, both right- and left-handed, are usually "capped" on each end by one or more secondary structures. Here, an in-depth classification of the diverse range of β-helix cap structures reveals subtle commonalities in structural components and in interactions with the β-helix core. Based on these uncovered commonalities, a toolkit of automated predictors was developed for the two distinct types of cap structures. In vitro deletion of the toolkit-predicted C-terminal cap from the pertactin β-helix resulted in increased aggregation and the formation of soluble oligomeric species. These results suggest that β-helix cap motifs can prevent specific, β-sheet-mediated oligomeric interactions, similar to those observed in amyloid formation.