The objective of this review was to evaluate the experimental approaches used in clinical trials to support the benefit claims of plant food supplements (PFS) with reported activity on infectious diseases. A literature search was conducted on a list of 309 plant species currently used in food supplements in Europe using the National Centre for Biotechnology Information (NCBI) PubMed Database to identify all the clinical trials for evaluating the benefit claim for preventing or treating infectious diseases in humans. The searches included a combination of terms related to the name of plants, class of infectious agents and therapeutic activities against infectious disease. By limiting the searches to clinical studies, only 27 articles representing 19 plant species were identified. From this list, 13 papers from the 10 plants most extensively researched were critically evaluated for assessing methods used to assess the benefits of PFS. Different study designs were used ranging from an open trial with no placebo or control and no randomization to double-blind randomized placebo controlled trials including a crossover design. Although the experimental approaches described in this review were found to be suitable for evaluating the benefit claims of PFS for treating infectious diseases caused by bacteria, viruses, fungi and parasites, the clinical study design should be more standardised as many studies lacked a control group and sufficient population size to be statistically acceptable taking into consideration patient variability. The reporting of the results varied and should also be standardised to include all the study parameters and data collected.