Electrochemical impedance spectroscopy (EIS) is the golden tool for many emerging biomedical applications that describes the behavior, stability, and long-term durability of physical interfaces in a specific range of frequency. Impedance measurements of any biointerface during in vivo and clinical applications could be used for assessing long-term biopotential measurements and diagnostic purposes. In this paper, a novel approach to predicting impedance behavior is presented and consists of a dimensional reduction procedure by converting EIS data over many days of an experiment into a one-dimensional sequence of values using a novel formula called day factor (DF) and then using a long short-term memory (LSTM) network to predict the future behavior of the DF. Three neural interfaces of different material compositions with long-term in vitro aging tests were used to validate the proposed approach. The results showed good accuracy in predicting the quantitative change in the impedance behavior (i.e., higher than 75%), in addition to good prediction of the similarity between the actual and the predicted DF signals, which expresses the impedance fluctuations among soaking days. The DF approach showed a lower computational time and algorithmic complexity compared with principal component analysis (PCA) and provided the ability to involve or emphasize several important frequencies or impedance range in a more flexible way.