In accordance with Thai wisdom, indigenous plant leaves have been used as food packaging to preserve freshness. Many studies have demonstrated that both antioxidant and antimicrobial activities contribute to protecting food from spoilage. Hence, the ethanolic extracts of leaves from selected plants traditionally used as food packaging, including Nelumbo nucifera (1), Cocos nucifera (2), Nypa fruticans (3), Nepenthes mirabilis (4), Dendrocalamus asper (5), Cephalostachyum pergracile (6), Musa balbisiana (7), and Piper sarmentosum (8), were investigated to determine whether they have antioxidant and antimicrobial activities against spoilage microorganisms and foodborne pathogens that might be beneficial for food quality. Extracts 1–4 exhibited high phenolic content at 82.18–115.15 mg GAE/g and high antioxidant capacity on DPPH, FRAP and SRSA assay at 14.71–34.28 μg/mL, 342.92–551.38 μmol Fe2+/g, and 11.19–38.97 μg/mL, respectively, while leaf extracts 5–8 showed lower phenolic content at 34.43–50.08 mg GAE/g and lower antioxidant capacity on DPPH, FRAP, and SRSA at 46.70–142.16 μg/mL, 54.57–191.78 μmol Fe2+/g, and 69.05–>120 μg/mL, respectively. Extracts 1–4 possessed antimicrobial activities against food-relevant bacteria, including Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, and Escherichia coli. Only N. mirabilis extract (4) showed antimicrobial activities against Salmonella enterica subsp. enterica serovar Abony and Candida albicans. Extracts 5–8 showed slight antimicrobial activities against B. cereus and E. coli. As the growth and activity of microorganisms are the main cause of food spoilage, N. fruticans (3) was selected for bioassay-guided isolation to obtain 3-O-caffeoyl shikimic acid (I), isoorientin (II) and isovitexin (III), which are responsible for its antimicrobial activity against foodborne pathogens. N. fruticans was identified as a new source of natural antimicrobial compounds I–III, among which 3-O-caffeoyl shikimic acid was proven to show antimicrobial activity for the first time. These findings support the use of leaves for wrapping food and protecting food against oxidation and foodborne pathogens through their antioxidant and antimicrobial activities, respectively. Thus, leaves could be used as a natural packaging material and natural preservative.