The unique glycan-binding ability of chemically synthesized boronic acid derivatives makes them emerging candidates for developing anti-influenza A virus (IAV) drugs. Herein we report the synthesis and the anti-IAV activities of three series of novel boronic acid-modified quindoline derivatives both in vitro and in vivo. Boronic acid-modified compounds 6a and 7a effectively prevented the entry of virus RNP into the nucleus, reduced virus titers in IAV infected cells, and also inhibited the activity of viral neuraminidase. Compound 7a possessed broad antiviral spectrum and was able to inhibit cellular NF-κB and MAPK signaling pathways to block IAV infection. More importantly, IAV infected mice treated with compound 7a showed better survival rates than mice treated with oseltamivir, a popular anti-IAV drug. Thus, our study provides not only an antiviral preclinical candidate but also useful information for further research and development of boronic acid-modified anti-IAV drugs.