Phytochemicals play a pivotal role in human health and drug discovery. The safety evaluation of plant extracts is a prerequisite to ensure that all phytochemicals are safe before translational development and human exposure. As phytochemicals are natural, they are generally considered safe, although this is not always true. The objective of this study was to investigate and compare the phytochemical composition, antioxidant potential, and safety evaluation of native Australian Muntries (Kunzea pomifera), Kakadu plum (Terminalia ferdinandiana), Davidson plum (Davidsonia) and Quandong peach (Santalum acuminatum) through the in vivo vertebrate zebrafish embryonic model. The highest total phenolic content (TPC; 793.89 ± 22.27 μg GAE/mg) was quantified in Kakadu plum, while the lowest TPC (614.44 ± 31.80 μg GAE/mg) was quantified in Muntries. Developmental alterations, mortality, and morbidity were assessed for toxicological screening of these selected native Australian fruit extracts. In this study, muntries were quantified as having the least LC50 value (169 mg/L) compared to Davidson plum (376 mg/L), Kakadu plum (>480 mg/L), and Quandong peach (>480 mg/L), which indicates that muntries extract was more toxic than other fruit extracts. Importantly, we found that adverse effects were not correlated to the total phenolic content and antioxidant potential of these native Australian fruits and cannot simply be predicted from the in vitro analysis. Conclusively, these selected native Australian fruit extracts are categorized as safe. This study could explore the use of these native Australian fruits in cosmetics, pharmaceuticals, and drug discovery.