The Internet of bio-nano things (IoBNT) is an emerging paradigm employing nanoscale (~1–100 nm) biological transceivers to collect in vivo signaling information from the human body and communicate it to healthcare providers over the Internet. Bio-nano-things (BNT) offer external actuation of in-body molecular communication (MC) for targeted drug delivery to otherwise inaccessible parts of the human tissue. BNTs are inter-connected using chemical diffusion channels, forming an in vivo bio-nano network, connected to an external ex vivo environment such as the Internet using bio-cyber interfaces. Bio-luminescent bio-cyber interfacing (BBI) has proven to be promising in realizing IoBNT systems due to their non-obtrusive and low-cost implementation. BBI security, however, is a key concern during practical implementation since Internet connectivity exposes the interfaces to external threat vectors, and accurate classification of anomalous BBI traffic patterns is required to offer mitigation. However, parameter complexity and underlying intricate correlations among BBI traffic characteristics limit the use of existing machine-learning (ML) based anomaly detection methods typically requiring hand-crafted feature designing. To this end, the present work investigates the employment of deep learning (DL) algorithms allowing dynamic and scalable feature engineering to discriminate between normal and anomalous BBI traffic. During extensive validation using singular and multi-dimensional models on the generated dataset, our hybrid convolutional and recurrent ensemble (CNN + LSTM) reported an accuracy of approximately ~93.51% over other deep and shallow structures. Furthermore, employing a hybrid DL network allowed automated extraction of normal as well as temporal features in BBI data, eliminating manual selection and crafting of input features for accurate prediction. Finally, we recommend deployment primitives of the extracted optimal classifier in conventional intrusion detection systems as well as evolving non-Von Neumann architectures for real-time anomaly detection.