The 2005 Ducati Multistrada 1000DS has a 992 cc air cooled 90° V-twin engine with a 40 degree included valve angle, based on Ducati's existing engines, with twin-spark plug heads, pressure fed plain camshaft bearings, redesigned crankshaft, higher oil pressure and volume, and new alloy clutch basket, drive and driven plates.

[4][6] Entry level Multistradas feature a number of individual components, like the double sided "Monster" style swing arm, the integrated die cast front and rear footrests, and the three spoke alloy wheels.

Suspension features Marzocchi 43 mm upside down front forks and a Sachs rear monoshock with adjustable preload and rebound.

The 2003 model Multistrada received most of its criticisms because of its seat, described as "a vinyl covered sheet of plywood" by Motorcyclist magazine, and windscreen that caused undue buffeting.

In 2005, the 1000DS Multistrada received an improved side stand (the 2003–2004 side stand was too short and made the bike prone to accidental tip-over), redesigned seats with softer padding and less angular shapes, improved mirrors with longer stems for better visibility and the optional touring screen from the 2003–2004 model year became standard.

2005 also saw the introduction of the 1000DS S model that came with Öhlins suspension, black wheels and carbon fiber belt covers and front fender.

It includes throttle by wire, a detuned version of the 1,200 cc liquid-cooled engine from the Ducati 1198 sportbike, and optional electronically adjustable suspension.

[8] With the third generation of Multistrada, Ducati focused particularly on the engine mechanics which includes a Testastretta DVT with 160 HP and 136 Nm of torque.

The most obvious concerns the new 1158 cm3 and 170 HP at 10,500 rpm V4 Granturismo engine: it is a four-cylinder that abandons the historic desmodromic distribution for a more classic spring return of the valves.

The V4 Granturismo engine adopts deactivation of the rear bank at idle so that there is no combustion in the cylinders, reducing consumption and improving thermal comfort thanks to lower temperatures.

An absolute first is the ARAS system featuring front and rear radar, through which it is possible to implement adaptive cruise control and blind spot detection.

With the 2022 model year, the Pikes Peak trim level returns, which is now clearly different from the rest of the range: the sporty characterization of the model includes the new single-sided swingarm (unpublished on the V4) and the 17" front wheel, combined with specific geometries for wheelbase, trail, steering head rake, raised footrests and narrower handlebars, and the "Race" configuration is making its debut on a Multistrada instead of the "Enduro" one, a mode recommended for circuit riding.