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Graphical abstract Highlights • Mono- and di-valent cations effects on morphology changes of lipid vesicles were investigated in both static and flowing environments. • Divalent cations cause significant aggregation or fusion of lipid vesicles, but monovalent cations have little effect on the vesicle morphology. • The order of the ability to destroy the vesicle morphology is Cu2+ > Mg2+ > Ca2+ > Na+ > K+. • Cation binding increases the net surface potential of lipid vesicles, leading to changes in the zeta potential. Abstract Lipid vesicles are an attractive model membrane experimental platform that is widely used in a biological context. The stability of vesicles can affect their performance and depends on various experimental conditions. How bio-related ions affect vesicle morphology is poorly understood in some cases. Herein, we investigated changes in vesicle morphology influenced by cation in the static and flowing environments. The effects of different mono- and di-valent metal cations on the morphology of lipid vesicles were systematically studied using the various techniques. The results showed that divalent cations caused significant aggregation or fusion of lipid vesicles, but monovalent cations had little effect on the vesicle morphology. Cation binding increased the net surface potential of vesicles, leading to changes in the zeta potential. The same qualitative kinetics were observed for cations that had the same valence at the same ionic strength. However, different types of cations gave different quantitative effects. The order of the ability to destroy the vesicle morphology was Cu2+ > Mg2+ > Ca2+ > Na+ > K+. These results are of practical value in the use of lipid vesicles as a bionic model, and help to shed light on the role of ions at membrane surfaces and interfaces. [ABSTRACT FROM AUTHOR]