A series consisting of new polyaminoisoprenyl derivatives were prepared in moderate to good chemical yields varying from 32 to 64% according to two synthetic pathways: (1) using a titanium-reductive amination reaction affording a 50/50 mixture of cis and trans isomers and (2) a direct nucleophilic substitution leading to a stereoselective synthesis of the compounds of interest. These compounds were then successfully evaluated for their <i>in vitro</i> antibiotic enhancer properties against resistant Gram-negative bacteria of four antibiotics belonging to four different families. The mechanism of action against <i>Enterobacter aerogenes</i> of one of the most efficient of these chemosensitizing agents was precisely evaluated by using fluorescent dyes to measure outer-membrane permeability and to determine membrane depolarization. The weak cytotoxicity encountered led us to perform an <i>in vivo</i> experiment dealing with the treatment of mice infected with <i>Salmonella typhimurium</i> and affording preliminary promising results in terms of tolerance and efficiency of the polyaminoisoprenyl derivative <b>5r</b>/doxycycline combination.